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I HC HU
TRNG I HC Y DC
CHU M CHI
NGHIN CU S LIN QUAN GIA NNG ENZYME MYELOPEROXIDASE HUYT TNG VI B DAY
LP NI TRUNG MAC NG MACH CANH VA MT S YU T NGUY C TIM MACH BNH NHN AI THAO NG TYP 2
LUN N TIN S Y HC
HU - 2016
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HU
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176TR, 15BIA
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I HC HU
TRNG I HC Y DC
CHU M CHI
NGHIN CU S LIN QUAN GIA NNG ENZYME MYELOPEROXIDASE HUYT TNG VI B DAY
LP NI TRUNG MAC NG MACH CANH VA MT S YU T NGUY C TIM MACH BNH NHN AI THAO NG TYP 2
Chuyn ngnh : NI TIT
M s : 62 72 01 45
LUN N TIN S Y HC
Ngi hng dn khoa hc:
1. GS.TS. NGUYN HI THY
2. PGS.TS. O TH DA
HU - 2016
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c c thnh qu ngy hm nay, ti nhn c nhiu s
quan tm gip ca c quan, qu Thy C, gia nh v bn b.
Li u tin, ti xin trn trng gi li cm n chn thnh n
Ban gim c i hc Hu, Ban gim hiu Trng i hc Y
Dc Hu, Ban gim c Bnh vin Trung ng Hu, Ban
gim c Bnh vin a khoa Trung tm Tin Giang, Ban Ch
nhim cng cc Thy, C, Anh, Ch ng nghip trong B mn
Ni- Trng i hc Y Dc Hu to mi iu kin thun
li v h tr ti trong qu trnh hc tp v nghin cu.
c bit ti xin by t lng knh trng v bit n su sc n
GS.TS Nguyn Hi Thy, PGS.TS o Th Da l
nhng ngi Thy tn tnh ging dy, du dt, gip , khch l
ti trong qu trnh hc tp, lm vic v nghin cu. Cc Thy
dnh nhiu thi gian, tr tu trc tip hng dn ti thc hin v
hon thnh lun n ny.
Ti cng xin chn thnh cm n ThS L Th Phng
Anh, ThS L Th Diu Phng v nhn vin khoa Ha Sinh
tn tnh gip v thc hin xt nghim nghin cu.
Ti cm n chn thnh n nhng bnh nhn, nhng ngi
ng tham gia cng trnh nghin cu ny.
Cui cng, bng nhng tnh cm thn thng nht xin dnh
cho Ba, M, Chng, cc Con v nhng ngi thn trong gia nh
cho ti im ta v ngun ng vin tinh thn qu gi nht.
Mt ln na xin trn trng v tri n n tt c mi ngi.
Hu, 2015
Chu M Chi
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LI CAM OAN
Ti xin cam oan rng: y l cng trnh nghin
cu ca ring ti. Cc s liu, kt qu trong lun n ny
l trung thc v cha tng c ai cng b trong bt k
mt cng trnh nghin cu no khc trc y.
K tn
Chu M Chi
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MC LC
Trang
Trang ph ba
Li cam oan
Mc lc
Ch vit tt
Danh mc cc bng
Danh mc cc biu , s , th
Danh mc cc hnh
T VN .................................................................................................. 1
Chng 1. TNG QUAN TI LIU ............................................................ 4
1.1. Bnh mch mu ln i tho ng tp 2 .......................................... 4
1.2. Yu t nguy c tim mch bnh nhn i tho ng tp 2 ................ 9
1.3. Enzyme myeloperoxidase .................................................................... 19
1.4. Cc phng tin thm d tn thng x va ng mch cnh ........... 32
1.5. Cc nghin cu v myeloperoxidase lin quan n ti ................... 38
Chng 2. I TNG V PHNG PHP NGHIN CU ............. 42
2.1. i tng nghin cu .......................................................................... 42
2.2. Phng php nghin cu ...................................................................... 43
Chng 3. KT QU NGHIN CU ........................................................ 59
3.1. Mt s yu t nguy c truyn thng ca i tng nghin cu .......... 59
3.2. Mt s yu t nguy c khng truyn thng ca i tng nghin cu ..... 63
3.3. in tim v siu m tim ....................................................................... 68
3.4. Nng myeloperoxidase (MPO) huyt tng ca i tng nghin cu .. 70
3.5. S lin quan gia mpo vi cc yu t nguy c tim mch bnh nhn
i tho ng ...................................................................................... 73
3.6. Mi tng quan gia mpo vi mt s yu t nguy c bnh nhn i
tho ng ............................................................................................ 78
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Chng 4. BN LUN ................................................................................. 89
4.1. Cc yu t nguy c tim mch truyn thng ca i tng nghin cu ..... 89
4.2. Cc yu t nguy c tim mch khng truyn thng ca i tng
nghin cu ............................................................................................ 98
4.3. in tim v siu m tim ..................................................................... 105
4.4. Nng enzyme mpo i tng nghin cu .................................. 108
4.5. S lin quan gia nng mpo huyt tng vi cc yu t nguy c
tim mch ............................................................................................ 112
4.6. S tng quan gia MPO v cc yu t nguy c .............................. 121
KT LUN .................................................................................................. 126
KIN NGH ................................................................................................. 128
DANH MC CC CNG TRNH KHOA HC LIN QUAN CNG B
TI LIU THAM KHO
PH LC
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CH VIT TT
- AGEs : Advanced glycation end products
(Cc sn phm cui ca ng ha bc cao)
- BMI : Body Mass Index
(Ch s khi c th).
- CTA : Computed Tomographic Angiography
(Chp mch ct lp vi tnh)
- DSA : Digital subtraction angiography
(Chp mch mu s ha xa nn)
- MV : ng mch vnh
- TB : i thc bo
- T : i tho ng.
- EF : Ejection fraction
(Phn sut tng mu)
- eNOS : Endothelial nitric oxide synthase
(Enzyme tng hp nitric oxide ni mc)
- HDL-C : High density lipoprotein cholesterol
(Cholesterol lipoprotein t trng cao)
- hs-CRP : High-sensitivity C-reactive protein
(Protein phn ng C nhy cao)
- LDL-C : Low density lipoprotein cholesterol
(Cholesterol lipoprotein t trng thp)
- LDLoxh : LDL oxy ha
- IMT : Intima-media thickness
(B dy lp ni trung mc).
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-LVMI : Left Ventricular Mass Index
(Ch s khi c tht tri)
- MACE : Major adverse cardiovascular event
(Bin c tim mch bt li chnh)
- MPO : Myeloperoxidase
- MRA : Magnetic Resonance Angiography
(Chp mch cng hng t)
- NMCT : Nhi mu c tim
- NO : Nitric oxide
- NOS : Nitric oxide synthase
(Enzyme tng hp nitric oxide)
- PAI-1 : Plasminogen activitor inhitor-1
(Cht c ch hot ha plasminogen 1)
- RLCNNM : Ri lon chc nng ni mc
- RLDN : Ri lon dung np
- RLLP : Ri lon lipid
- ROS : Reactive oxygen species
(Cc mu oxy phn ng)
- TC : Total cholesterol
(Cholesterol ton phn)
- TG : Triglycerid
- THA : Tng huyt p
- TMCT : Thiu mu c tim
- VB : Vng bng
- WHO : World Health Organization
(T chc Y t Th gii)
- XVM : X va ng mch.
- YTNC : Yu t nguy c
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DANH MC CC BNG
Trang
Bng 2.1. Phn bo ph p dng cho ngi Chu - Thi Bnh Dng .... 48
Bng 3.1. Phn b t l tui v gii ca i tng nghin cu .................... 59
Bng 3.2. Phn b tnh trng THA nhm bnh ......................................... 60
Bng 3.3. c im chung v lipid mu nhm bnh ................................. 61
Bng 3.4. T l ri lon lipid mu nhm bnh ........................................... 61
Bng 3.5. T l kim sot lipid mu theo mc tiu nhm bnh ................. 62
Bng 3.6. Cc ch s sinh x va nhm bnh............................................ 62
Bng 3.7. Cc ch s sinh x va nguy c nhm bnh .............................. 63
Bng 3.8. c im BMI nhm bnh ........................................................... 63
Bng 3.9. T l bo ph dng nam nhm bnh ........................................... 64
Bng 3.10. c im glucose i v HbA1C nhm bnh ........................... 64
Bng 3.11. c im v CRP nhm bnh ................................................... 65
Bng 3.12. c im v Fibrinogen huyt tng nhm bnh ..................... 65
Bng 3.13. c im v bch cu nhm bnh ................................................ 66
Bng 3.14. c im v b dy ng mch cnh (IMT) nhm bnh ............. 66
Bng 3.15. T l x va ng mch cnh nhm bnh ................................. 67
Bng 3.16. c im v QTc in tim nhm bnh .................................. 68
Bng 3.17. c im v ch s Sokolow-Lyon in tim nhm bnh .......... 68
Bng 3.18. c im v thiu mu c tim trn in tim nhm bnh .......... 69
Bng 3.19. c im v ch s khi c tht tri (LVMI) nhm bnh ......... 69
Bng 3.20. c im v EF nhm bnh ...................................................... 70
Bng 3.21. Nng MPO ca nhm chng ................................................... 70
Bng 3.22. Nng MPO ca nhm bnh ..................................................... 71
Bng 3.23. T l tng MPO X 2SD ca nhm bnh v nhm chng ........ 72
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Bng 3.24. Lin quan gia MPO vi tui, thi gian pht hin bnh v
THA nhm bnh ........................................................................ 73
Bng 3.25. Lin quan MPO vi lipid mu v cc ch s lipid nhm bnh .. 74
Bng 3.26. Lin quan gia MPO vi vng bng v ch s khi c th .......... 75
Bng 3.27. Lin quan MPO vi ng huyt ................................................. 75
Bng 3.28. Lin quan MPO vi cc yu t vim ............................................ 76
Bng 3.29. Lin quan gia MPO vi IMT < 0,9 v IMT 0,9mm ................ 76
Bng 3.30. Lin quan gia MPO vi mng x va ........................................ 77
Bng 3.31. Lin quan MPO vi bt thng trn in tim .............................. 77
Bng 3.32. Lin quan gia MPO vi EF v LVMI trn siu m tim ............. 78
Bng 3.33. Tng quan gia MPO vi mt s yu t nguy c truyn thng .... 78
Bng 3.34. Tng quan gia MPO vi mt s yu t nguy c khng
truyn thng .................................................................................. 79
Bng 3.35. Tng quan gia MPO vi bin chng tim ................................. 81
Bng 3.36. Tng quan hi quy tuyn tnh a bin gia MPO vi cc YTNC .. 82
Bng 3.37. Din tch di ng cong ROC gia MPO vi vng bng
tng ng vi MPO330pmol/l ................................................... 83
Bng 3.38. Din tch di ng cong ROC gia MPO vi BMI tng
ng vi MPO330pmol/l ............................................................. 84
Bng 3.39. Din tch di ng cong ROC gia MPO vi IMT tng
ng vi MPO330pmol/l ............................................................. 85
Bng 3.40. Din tch di ng cong ROC gia MPO vi QTc tng
ng vi MPO330pmol/l ............................................................. 86
Bng 3.41. Ch s nguy c gia MPO vi IMT ............................................. 87
Bng 3.42. Ch s nguy c gia MPO vi mt s yu t ............................... 88
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DANH MC CC BIU , S
Trang
Biu
Biu 3.1. Thi gian pht hin bnh i tho ng theo cc nhm. ....... 60
Biu 3.2. T l dy lp ni trung mc ng mch cnh nhm bnh ..... 67
Biu 3.3. So snh nng MPO ca nhm bnh v nhm chng .......... 71
Biu 3.4. Tng quan gia MPO v vng bng ...................................... 79
Biu 3.5. Tng quan gia MPO v BMI ................................................ 80
Biu 3.6. Tng quan gia MPO v IMT ................................................ 80
Biu 3.7. Tng quan gia MPO v mng x va .................................. 81
Biu 3.8. Tng quan gia MPO v QTc ................................................ 82
Biu 3.9. ng cong ROC gia MPO vi vng bng ........................... 83
Biu 3.10. ng cong ROC gia MPO vi BMI .................................... 84
Biu 3.11. ng cong ROC gia MPO vi IMT .................................... 85
Biu 3.12. ng cong ROC gia MPO vi QTc ..................................... 86
Biu 3.13. ng cong ROC gia MPO vi IMT, VB, BMI v QTc ...... 87
S
S 1.1. C ch gy x va ng mch ca LDL nh, m c ................ 11
S 1.2. Tc ng ca tng ng huyt v khng insulin ln to NO ...... 14
S 1.3. Tc ng gia vim, khng insulin v x va ng mch ............ 16
S 2.1. Cc bc tin hnh nghin cu ..................................................... 57
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DANH MC CC HNH
Trang
Hnh 1.1. Cu trc enzyme myeloperoxidase ............................................... 20
Hnh 1.2. Phn ng to ra hypochlorite ........................................................ 20
Hnh 1.3. Tin trnh x va ng mch lin quan MPO .............................. 23
Hnh 1.4. Tc ng ca HOCl ln tho cp NOS to gc t do superoxide .... 27
Hnh 1.5. Tc dng bt li ca myeloperoxidase ......................................... 28
Hnh 1.6. C ch ca MPO trong x va ng mch ................................... 29
Hnh 1.7. C ch MPO tng tc vi gc t do chn lc nh hng bt li
trong lp ni mc .......................................................................... 31
Hnh 1.8. B dy lp ni trung mc ng mch cnh chung bn tri
dy 2,8mm .................................................................................... 32
Hnh 1.9. Hnh nh mng x va ng nht ................................................. 33
Hnh 1.10. Cc lp ca thnh ng mch trong qua IVUS ............................ 34
Hnh 1.11. Chp MRA ca ng mch cnh trong ........................................ 35
Hnh 1.12. Hnh chp CTA ng mch cnh ................................................. 36
Hnh 1.13. Chp DSA ng mch cnh trong ................................................ 37
Hnh 2.1. V tr t u d o IMT ng mch cnh.................................... 49
Hnh 2.2. Cch o b dy lp ni trung mc (IMT) ..................................... 51
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T VN
1. TNH CP THIT CA TI NGHIN CU
i tho ng l mt bnh l ni tit chuyn ha ph bin, ngy cng
c khuynh hng gia tng trn khp th gii cng nh nc ta v ang tr
thnh mt thch thc chnh trong Th k XXI [4], [42], [171]. y l mt
nhm bnh chuyn ha vi c trng l tng glucose mu do thiu ht tng
i hay tuyt i v tit v hay l tc dng ca insulin trn t bo ch.
Khi ni n bnh i tho ng nht l i tho ng tp 2 ngi ta
thng lin tng n bin chng tim mch trong l tn thng mch mu
ln thng gp nh bnh l mch mu no, ng mch vnh v ng mch
hai chi di. Bin chng mch mu ln trong i tho ng thc cht l mt
th x va ng mch v i tho ng lin quan ti ri lon chuyn ha bao
gm tng glucose mu, tng huyt p, ri lon lipid v khng insulin [86].
X va ng mch bnh nhn i tho ng tp 2 xy ra sm hn, nng
hn, lan rng hn so vi ngi khng b bnh i tho ng v nh hng
khng nhng n cc ng mch gn m cn v tr xa gc. Cc bin chng
mch mu ln lm tng nguy c tai bin mch mu no cao gp 2 4 ln
ngi i tho ng so vi ngi khng b i tho ng [45]. Bin c
mch vnh l nguyn nhn hng u gy t vong trn bnh nhn i tho
ng (hn 65%) v tn thng ng mch hai chi di v ang tr thnh
nguyn nhn chnh gy ct ct chi bnh nhn i tho ng [36].
Bn cnh cc yu t nguy c truyn thng gy x va ng mch nh
bo ph, tng huyt p, tng glucose mu mn tnh, ri lon lipid mu
gy nhng bt thng thnh mch, ri lon chc nng ni mc mch mu,
tng ngng tp tiu cu v tng ng mu dn n nguy c tn thng mch
mu ln. Gn y vai tr ca cc yu t nguy c khng truyn thng c
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cp nh cht c ch hot ha plasminogen-1, protein phn ng C,
microalbumin niu...[86] v nht l myeloperoxidase c nghin cu ghi
nhn c lin quan n x va ng mch nhng i tng c nguy c cao
trong c bnh i tho ng [106].
Vim v stress oxy ha ng vai tr quan trng trong tin trnh x va
ng mch [88]. Myeloperoxidase l enzyme c tit ra t bch cu, hot
ng nh yu t vim v stress oxy ha. Myeloperoxidase c vai tr quan
trng trong tin trin x va ng mch. C ch gy x va ng mch ca
myeloperoxidase th hin bng nhiu con ng bao gm myeloperoxidase
hot ng nh cht xc tc lm tng LDL oxy ha, kt qu lm tng thu nhn
LDL vo lp ni mc, gp phn hnh thnh v pht trin t bo bt, hnh
thnh mng bm; lm ri lon chc nng bo v ni mc ca HDL a n
ri lon chc nng ni mc; Myeloperoxidase trc tip qut dn nitric oxide,
hn ch sinh kh dng ca NO dn n co mch v thc y tn thng ni
mc mch. Ri lon chc nng ni mc pht trin sm trong giai on sm
ca i tho ng trc khi biu hin lm sng bng x va ng mch.
Gim nitric oxide v tng stress oxy ha l nhng yu t quan trng trong
sinh bnh hc ca bin chng i tho ng. Cc mu oxy ha phn ng
ng vai tr quan trng trong ri lon chc nng ni mc qua trung gian tng
ng huyt v bin chng mch mu. Myeloproxidase l du ch im cho
ri lon chc nng ni mc v l cht to ra cc mu oxy ha phn ng tng
trong i tho ng. Nng myeloperoxidase tng bnh nhn i tho
ng tp 2 c ghi nhn.
Bin chng tim mch l nguyn nhn gy t vong hng u ngi b
i tho ng. V vy vic nghin cu cc yu t nguy c tim mch bnh
nhn i tho ng lun thu ht c s quan tm ca cc nh chuyn mn.
Do lm th no pht hin sm v iu chnh kp thi cc yu t nguy c
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tim mch l iu rt quan trng v n gip ngi bnh nng cao cht lng
cuc sng v ko di tui th.
Song song vi vic pht hin yu t nguy c, nhiu phng php
nh gi x va ng mch giai on sm nh o dy lp trung ni mc
ng mch cnh qua siu m l phng php khng xm nhp, c nhy
cao cng c ng dng trn lm sng. Chng trnh gio dc cholesterol
quc gia v Hip hi Tim mch Hoa K chp thun o b dy lp ni
trung mc ng mch cnh nh gi nguy c tim mch [45].
Lin quan gia nng myeloperoxidase huyt tng v bt thng
cu trc ni mc mch mu ngoi bin bnh nhn i tho ng tp 2
ti Vit Nam cha thy cp. Xut pht l do trn chng ti tin hnh
nghin cu ti ny.
2. MC TIU NGHIN CU
2.1. Xc nh mt s yu t nguy c tim mch, b dy lp ni trung mc ng
mch cnh v nng myeloperoxidase huyt tng trn bnh nhn i tho
ng tp 2.
2.2. nh gi mi lin quan v tng quan gia nng myeloperoxidase
huyt tng vi b dy lp ni trung mc ng mch cnh v mt s yu t
nguy c tim mch truyn thng (tui, tng huyt p, ri lon lipid mu) v
khng truyn thng (HbA1C, CRP, fibrinogen huyt tng, bch cu..) trn
nhng bnh nhn i tho ng tp 2 ny.
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Chng 1
TNG QUAN TI LIU
1.1. BNH MCH MU LN I THO NG TP 2
1.1.1. Dch t hc i tho ng tp 2 v bin chng tim mch
i tho ng (T) tp 2 l mt bnh ri lon chuyn ha vi c
trng bi tng glucose mu mn tnh, khng insulin v thiu insulin
nhiu mc khc nhau. T tp 2 thng khng c chn on nhiu
nm trc do biu hin lm sng kn o. Tuy nhin ngay trong giai on
thm lng ny bnh c nguy c bin chng mch mu.
T tp 2 chim trn 90% cc trng hp T [42], ang ngy cng
gia tng trn ton th gii trong c Vit Nam v ang tr thnh mt thch
thc ca y hc. Theo T chc Y t Th gii nm 2000 c khong 157,3 triu
ngi mc bnh T v d bo n nm 2025 con s ny s l 300 triu
ngi [4]. Theo Lin on T Quc t nm 2011 c khong 366 triu ngi
mc bnh T v c on n nm 2030 s ngi mc bnh T l 552
triu, ring Vit Nam nm 2011 c 1,7 triu ngi mc bnh T th n
nm 2030 s ln n 3,1 triu ngi ln tui t 20-79 mc bnh T [171].
T chu chim hn 60% v Vit Nam l mt trong 10 quc gia c s
ngi mc bnh T cao nht Chu [65].
Khi ni n T tp 2 ngi ta thng lin tng n bin chng tim
mch [49]. Bin chng tim mch l nguyn nhn chnh gy t vong, tn
ph v tn km nht trong chi ph trc tip v gin tip bnh nhn T.
Nguyn nhn t vong bnh nhn T tp 2 do chng mch mu ln
chim 75% [138]. Theo Hip hi Tim mch Hoa K T c xem
tng ng nh mt bnh mch vnh [104]. Trong nghin cu East-West
Study Phn Lan ko di 7 nm cho thy t l nhi mu c tim gp 6 ln
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bnh nhn T so vi khng T. Mt nghin cu on h theo di 18
nm ghi nhn bnh nhn T khng c thiu mu c tim trc c nguy
c t vong do bnh l tim mch cao hoc nguy c cao hn bnh nhn
khng c T m c nguy c thiu mu c tim trc [42].
1.1.2. C ch bnh mch mu ln bnh nhn i tho ng
Bin chng mch mu ln trong T thc cht l mt th x va ng
mch (XVM) v T c lin quan ti ri lon chuyn ha bao gm tng
glucose mu, tng huyt p, ri lon lipid v khng insulin. Bin chng
mch mu ln nh nhi mu c tim, t qu thng xy ra t ngt nhng
XVM hin din trong thi gian di v khng c triu chng.
S tin trin ca XVM bnh nhn T tp 2 c mt s c im
nh bt thng v chc nng ni mc mch mu xut hin sm, tng hot
ng ca tiu cu, thc y tng sinh t bo c trn v c cht sau khi ng
mch b tn thng, khuynh hng ti to mch mu bt li, tn thng s
thoi bin fibrin vi khuynh hng to huyt khi v phn ng vim.
1.1.2.1. Ri lon chc nng ni mc mch mu
Ri lon chc nng ni mc (RLCNNM) l du hiu sm ca tn thng
XVM v xy ra rt sm ngay t giai on tin T bnh nhn T tp 2
c l lin quan n tng glucose mu, tng huyt p, ri lon lipid mu v
khng insulin. V th RLCNNM l du ch im sm ca bin chng vi mch
v mch mu ln ca T tp 2 [36].
T bo ni mc sn xut nhiu cht trung gian ha hc trong c nitric
oxide (NO) l cht gin mch ph thuc ni mc c vai tr iu ha trng
lc mch mu. V phng din sinh hc, RLCNNM bnh nhn T tp 2
rt a dng lin quan n NO nh gim sn xut NO, NO b bt hot bi cc
mu oxy phn ng (reactive oxygen species- ROS), ri lon s sao chp NO.
Tng glucose mu lm hot ha protein kinase C thng qua tng stress oxy
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ha, sn xut cht diacylglycerol hoc cc sn phm cui ca s ng ha
bc cao (AGEs- advanced glycation end products) [66], [163]. Con ng
chuyn ha protein kinase C c c trng v lin quan vi mt vi bt
thng chc nng t bo, bao gm gia tng co mch v RLCNNM qua trung
gian endothelin 1, angiotensin II, enzyme NO synthase ni mc (endothelial
nitric oxide synthase-eNOS) [36].
RLCNNM cn lin quan n cc cytokin vim. Mt s nghin cu cho
thy c mi lin quan gia nng cc cytokin nh cht interleukine-6 (IL-6) v
CRP vi s pht trin T tp 2 v bo ph dng nam [36], [88].
1.1.2.2. Tng hot tnh tiu cu
Chc nng tiu cu bnh nhn T bt thng nh tng dnh, qu
nhy cm vi cc cht tin kt dnh, tng prostaglandin v thromboxan A2,
i sng tiu cu gim [11]. Tiu cu thng c kch thc ln hn, c s
lng th th glycoprotein (GP)IIb/IIIa nhiu hn v trn thc nghim ghi
nhn s ngng tp sn sng hn so vi ngi khng T [36]. Cc yu t
ny gp phn lm tng hot tnh tiu cu bnh nhn T tp 2 [86].
Knobler v cng s ghi nhn kt dnh v ngng tp tiu cu tng bnh
nhn T hn khng T. Sheachter v cng s chng minh mc glucose
huyt tng l yu t ch yu tin on huyt khi ph thuc tiu cu. Nng
glucose, apolipoprotein B v magnesium ni bo tng quan vi huyt
khi ph thuc tiu cu bnh nhn c bnh l mch vnh n nh [21].
Prostacyclin (PGI2) v NO l 2 phn t c trng vi thuc tnh chng
ngng tp tiu cu, c phng thch t ni mc mch mu v c ch cc
tc dng ca mt s tc nhn tin ngng tp. S suy gim hot ng chng
ngng tp ca PGI2 v NO ng vai tr then cht trong bnh sinh ca chc
nng tiu cu T tp 2. Hn na cc cht tin ngng tp c dn cht t
tiu cu b iu ha ngc bnh nhn T tp 2 v khng insulin lm
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bnh nhn T tp 2 c khuynh hng c huyt khi qua trung gian tiu
cu [36]. Gorudko v cng s cho thy MPO tc ng gin tip lm tng
hot ng ca tiu cu [91].
Do bt thng chc nng tiu cu ni trn, c nhiu nghin cu cho
thy vic s dng thuc chng ngng tp, cc dn cht thienopyridin v c
ch th th GPIIb/IIIa c li l ci thin bin c tim mch. iu chnh trc
GPIIb/IIIa bnh nhn T tp 2 c hi chng mch vnh cp v/ hoc l
can thip mch vnh qua da lm ci thin d hu cho bnh nhn T [36].
1.1.2.3. Tng sinh t bo v lng ng c cht ni mc mch mu
Bnh nhn T tp 2 c t l ti hp cao hn bnh nhn khng T sau
khi can thip ng mch vnh qua da c ghi nhn qua cc nghin cu.
S ti hp mch mu sau khi nong bng bng l do s tc nghn mch mu
t ngt, ti to ng mch bt li v tng sinh tn to ni mc ng mch.
S ra i ca gi (stent) ci thin t l thng mch mu do lm
gim tn sut ti hp bnh nhn T hoc khng T bng cch loi tr
s tc nghn mch mu t ngt, ti to ng mch bt li sau khi can thip
ng mch vnh qua da [36]. Trong th nghim Stent-PAMI, bnh nhn T
b nhi mu c tim cp c t stent gim ng k t l phi ti to mch mu
v t l cc bin chng tim mch chnh. Tuy nhin, t l ti hp nhm T
cao hn nhm khng b T [39].
Ti hp sau t stent cn lin quan tng sinh tn to ni mc mch. C
insulin ln glucose u lin quan n tng sinh tn to ni mc mch T
tp 2. Tng glucose mu tc ng n cc yu t tng trng nh yu t tng
trng nguyn bo si v yu t tng trng chuyn dng alpha. Tng
glucose mu lm tng s tng hp cc thnh phn cht nn, gim sn xut
cht heparin sulfate dn n gim c ch tng sinh t bo. Tng glucose to
nhiu cht AGEs, cht gy tng sinh t bo v tuyn m t bo vim. Bin i
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8
cht AGEs v th th ca chng lm gim ng k tng sinh tn to ni mc
mch trong nghin cu ti hp mch chut Zucker khng insulin.
Mc d vai tr sinh hc ca insulin cha r, khng insulin thng phi
hp vi ti hp mch mu. Mt nghin cu gn y ghi nhn khng insulin
gia tng nguy c ti hp sau nong mch vnh qua da [36].
1.1.2.4. Ti to ng mch bt li
Bnh nhn T thng biu hin s tin trin XVM bao gm khuynh
hng ti to mch bt li trong nhng giai on u ca XVM, thiu s
hnh thnh tun hon ph v tng nguy c tc nghn mch mun sau khi nong
vnh bng bng.
Glagov v cng s ghi nhn hin tng gin ng mch cn b sm hin
din lp ni mc ca giai on u XVM ng mch vnh thn chnh
tri (left main trunk) ca xc cht. S gin mch cn b ny ln n 40%.
Nhng bnh nhn T thay v c s p ng gin ng mch thch nghi th
li c biu hin co tht mch lm cho lng mch c mng va hp ng k. V
vy, ng mch vnh ca bnh nhn T thng nh hn, chiu di tn
thng di hn v bnh l c tnh cht lan ta. y l nt c trng v hnh
thi lm tng t l bin chng sau can thip ng mch vnh qua da [36].
Bnh nhn T vi bnh l ng mch in hnh ny lm t l tc
nghn ng mch mun cn cao d c nong vnh bng bng. Van
Belle ghi nhn nghn mch mu mun chim t l 15% sau nong vnh bng
bng. Ti hp tc nghn c nguy c t vong tim mch trong vng 10 nm
cao. Marso v cng s nghin cu 673 bnh nhn c hi chng mch vnh
cp c can thip ti thng ng mch vnh qua da, trong c 119 bnh
nhn T, theo di trung bnh l 3,4 nm th bnh nhn T c ti nhp
vin, ti thng mch mu nhiu hn, tn thng mng x va ln hn, di
hn v lng mch cng hp hn so vi khng c T [122].
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9
1.2. YU T NGUY C TIM MCH BNH NHN I THO
NG TP 2
Bnh l tim mch l nguyn nhn chnh gy t vong bnh nhn
T tp 2. Ngoi cc yu t nguy c (YTNC) truyn thng th bnh nhn
T tp 2 cn c cc YTNC khng truyn thng [131].
1.2.1. Cc yu t nguy c truyn thng
1.2.1.1. Tng huyt p
T v tng huyt p (THA) l 2 bnh l bn ngoi c v khc bit
nhng thc t thng xy ra trn cng bnh nhn T, c bit bnh nhn
T tp 2. THA trong T tp 2 thng l mt trong nhng biu hin
ca hi chng chuyn ha, khng insulin. Phi hp THA v T lm gia
tng nguy c bin chng v t vong tim mch bnh nhn T [48]. C t
nht 88% bnh nhn T c THA c iu tr hoc khng kim sot. THA
khng nhng c tn sut cao ngi T m cn tin on tin trin ca
T. Mt khi THA c chn on, nguy c T trong 5 nm tip theo
gp 2,5 ln [42].
Nghin cu Whitehall Anh theo di trong 10 nm, nguy c t vong do
bnh tim mch bnh nhn T c THA nhiu hn, tn sut THA T
tp 2 tng 2,5 ln so vi ngi khng T. THA nguyn pht pht trin
thnh T l do ri lon thnh phn t chc c vn (nhiu m v gim cc
si co c nhy cm chm vi insulin), gim lu lng mu n t chc c
lm mch mu ph i, tha tht, co mch v ri lon p ng iu ha hu
th th i vi insulin [36].
1.2.1.2. Ri lon lipid mu
Ri lon lipid (RLLP) mu l yu t quan trng gy XVM bnh nhn
T nht l T tp 2, lin quan n thiu insulin v hay l khng
insulin [35]. T l RLLP bnh nhn T tp 2 cao gp 2-3 ln so vi ngi
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10
khng bnh T [5],[140]. RLLP hin din ngay c khi c bt thng dung
np glucose. iu ny nguy him cho nhng i tng ny l ch h khng
bit mnh b mc bnh phng v mc nguy c vi tai bin tim mch
ca h khng khc g so vi ngi mc bnh T tp 2 [5].
Nhiu nghin cu chng minh t l nhi mu c tim, cn au tht ngc
bnh nhn T cao hn bnh nhn khng T. T l ny tng song hnh vi
tng nng lipid mu. Nghin cu UKDPS cho thy T c tng cholesterol
lipoprotein t trng thp (low density lipoprotein cholesterol ; LDL-C), tng
triglycerid, gim cholesterol lipoprotein t trng cao (high density lipoprotein
cholesterol ; HDL-C) trong mu. Nhng ri lon ny lun kt hp vi tng nguy
c mc bnh mch vnh. Tin lng bnh l mch vnh c ci thin ng k,
thm ch gim c t vong do mch vnh nh iu chnh c cc RLLP [5].
RLLP mu l YTNC bnh nhn T thng c bt thng v cht lng
lipoprotein lin quan ti khng insulin. RLLP bnh nhn T c c trng
l tng triglycerid v nng HDL-C huyt tng thp. Nng LDL-C ngi
khng insulin khng khc bit vi ngi cn nhy insulin. Tuy nhin c s thay
i cht lng trong ht LDL l ht LDL nh hn d b oxy ha lm cho qu trnh
XVM s mnh hn. LDL kch thc nh, m c ngm vo thnh ng mch
nhanh hn v kt li ti protein glycat ha hn so vi cc ht LDL ln hn [96].
khng m m do tng hot ng hormon nhy lipase v lm tng
tan v triglycerid d tr. Cc acid bo t do gii phng t t bo m c vn
chuyn ti gan tng hp triglycerid v cholesterol lipoprotein t trng rt
thp (very low density lipoprotein cholesterol VLDL). S gia tng VLDL
thay i t HDL-C lm HDL-C trong huyt tng thp. Ni cch khc acid
bo t do tng c vai tr trong khng insulin [57].
Hin nay triglycerid bnh nhn T tp 2 c quan tm, bnh tim
thiu mu lin quan triglycerid. Tng triglycerid lc i lin quan n tai bin
mch vnh T tp 2 v nhm c ri lon dung np glucose [36].
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11
S 1.1. C ch gy x va ng mch ca LDL nh, m c [36]
1.2.1.3. Ht thuc l
Ht thuc l l yu t nguy c gy XVM c th thay i c. Ht
thuc l lin quan cc yu t vim, cc du ch im lm gim chc nng
ni mc, tng stress oxy ha. Ht thuc l cn lm tng kt dnh tiu cu,
tng nht v lm tng ng. Ngi ht thuc l c khng insulin cao
hn ngi khng ht thuc l, nng HbA1C cao v cung cp oxy cho
cc m thp [165]. Bnh nhn T c ht thuc l lm nguy c bnh tim
mch, t vong sm tng v tng t l bin chng vi mch trn T. Cc phn
tch gp cho thy ht thuc l lm tng pht trin T tp 2, nguy c b T
ln n 44%. Ht thuc l lm khng insulin v p ng tit insulin khng
y . Mt nghin cu bnh nhn T tp 2 mi chn on c ht thuc
l khi ngng ht thuc l trong 1 nm s ci thin cc thng s chuyn ha,
gim huyt p v gim albumin niu [65].
1.2.2. Cc yu t nguy c khng truyn thng
1.2.2.1. khng insulin
Cc nghin cu tin cu cho thy tng insulin mu l YTNC quan trng
trong bnh thiu mu c tim. Nghin cu Quebec Heart 1898 nam t 45-
76 tui, khng c thiu mu c tim, trong 5 nm theo di c 114 nam b
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12
thiu mu c tim, nng insulin tng 18% so vi chng. Nghin cu
Helsinki Policemen Study trn 970 cnh st nam theo di t vong trong 22
nm cng ghi nhn tng insulin mu lin quan vi tt c nguyn nhn tng
t vong tim mch c lp vi cc YTNC khc. Mt phn tch gp ca Marja
Pyorala v cng s cc YTNC c trong thnh phn trng tm ca hi chng
khng insulin 164 bnh nhn nam c bin c tim mch v 70 nam b t
qu. Kt qu cho thy ch c yu t khng insulin d on nguy c t
qu v bnh tim mch c lp vi cc YTNC khc. Nhn chung, cc nghin
cu cho rng thnh phn ca hi chng c mt trong nhiu nm trc khi
khi pht bnh T tp 2 v "ng h cho bnh tim mch bt u hn gi
trc khi khi pht T lm sng".
C ch khng insulin lin quan vi cc YTNC tim mch khc biu
hin trong hi chng chuyn ha nh bo ph, THA, RLLP mu, bt thng
tn hiu insulin v tng insulin mu. khng insulin l bt thng ch yu
ni kt T tp 2 v bnh tim mch, n lin kt gn vi YTNC tim mch
truyn thng v cng lin quan ng k vi cc YTNC khng truyn thng.
Bo ph
Theo WHO (1998): Bo ph hin ang l mt i dch ti cc quc gia
pht trin v ang gia tng nhanh chng nhiu nc ang pht trin, c
bit l vng Chu - Thi Bnh Dng [29]. Trong s nhng ngi tr T
c khong 10,4% tha cn v 79,4% bo ph [48].
Bo ph lin quan ti mt lot cc YTNC ca XVM v bnh tim
mch gm THA, khng insulin, ri lon dung np ng, cholesterol
cao, tng triglycerid, gim HDL-C, tng fibrinogen huyt tng, RLCNNM
v vim. Kt qu t nhng nghin cu Framingham, Nurses Health Study
v mt s nghin cu khc cho thy tng quan thun gia bo ph v bnh
mch vnh.
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13
T bo m c kh nng tng hp v tit ra cc cht nh adiponectin,
resistin, leptin, PAI-1, yu t hoi t u alpha (Tumor necrosis factor-, TNF-
) v interleukin-6 (IL-6) [32].
Adiponectin tham gia vo iu ha tnh nhy cm ca insulin v qu
trnh oxy ha lipid. Adiponectin lin c tc dng chng XVM, chng vim.
Ngi bo ph th adiponectin gim, ngc li khi gim cn th nng
adiponectin tng [32]. Resistin l mt protein c lin quan n khng insulin.
Resistin tng gy khng insulin v ngc li. Bo ph ni tng lin quan vi
tng PAI-1. Cht hot ha plasminogen thp so vi PAI-1 l mt yu t tin on
cho bnh tim mch. Tng insulin s kch thch sn xut PAI-1 v mc yu t x va
ny cao trong T tp 2 khng insulin.
M m c xem l c quan ni tit tit nhiu loi hormone v cytokin.
Nhiu nghin cu cho thy c mi lin quan gia bo ph v CRP, TNF v
IL6 v cc cytokine ny tin on cho bnh tim mch. CRP huyt tng tng
ngi bo ph c c trng khc ca hi chng chuyn ha. ngi bo
ph tng TNF trong m m. TNF thc y bch cu n nhn tng kt dnh
vo ni mc v c ch enzyme tng hp NO (NOS). IL-6 c l cng thc y
cc cytokin ni mc lm RLCNNM [86].
1.2.2.2. Ri lon chc nng ni mc mch mu
RLCNNM l bt thng sm trong din tin t nhin ca bnh tim mch
v c th l yu t tin on sm bin c tim mch [150]. Tm quan trng ca
n trong T c cng nhn.
Caballero v cng s nghin cu phn ng mch mu cng nh cc du
hiu sinh ha ca chc nng ni mc 143 ngi, tui t 25-70, chia thnh 4
nhm. Nhm 1 gm 30 ngi khe mnh c glucose bnh thng, tin s gia
nh khng bnh T; nhm 2 gm 39 ngi khe mnh c glucose bnh
thng, tin s cha hoc m b T; nhm 3 gm 32 ngi ri lon dung np
(RLDN) glucose v nhm 4 gm 42 bnh nhn T tp 2 khng bin chng
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14
mch mu. Gin mch p ng vi acetylcholine chloride gim nhm
RLDN glucose v T so snh vi nhm chng; endothelin-1 nhm chng
cao hn cc nhm; vWF ch cao nhm T; phn t bm dnh ni bo
(intracellular adhesion molecule-ICAM) cao trong nhm RLDN glucose v
T; ngc li phn t kt dnh t bo mch mu (vascular cell adhesion
molecule-VCAM) cao trong nhm tin s gia nh c T v nhm c T.
iu ny phn nh bt thng phn ng mch mu v du hiu sinh ha ca
hot ha t bo ni mc hin din sm ngi nguy c pht trin T tp 2,
ngay c giai on dung np glucose bnh thng [63].
Khng insulin bnh nhn T tp 2 gy tnh trng RLCNNM c
chng minh. Insulin tc ng qua 2 c ch: trc tip v insulin l cht truyn
tin th 2 trong qu trnh tng hp NO c s v gin tip qua hot ho tng
hp NO theo con ng t L- arginin. Trong tnh trng khng insulin, s sn
xut NO b gim xung ng thi c s tng sn xut cc acid bo t do nn
cng lm suy gim chc nng t bo ni mc [105].
i tho ng tp 2
Tng ng huyt khng insulin
Hot ng arginase Hot ng NOS
Ornithine + Urea Arginase L-Ariginin --- NOS- NO + L-Citrulline
NO v ROS
khng insulin
Vim
Ri lon chc nng ni mc
X va ng mch
S 1.2. Tc ng ca tng ng huyt v khng insulin ln to NO [105]
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15
1.2.2.3. Ri lon tiu si huyt
H thng tiu si huyt ni sinh c s cn bng gia hot ha plasminogen
m (tPA) v PAI-1. c ch qu mc tiu si huyt s lm ng mu v huyt
khi gy bin c tim mch. Hot ng v nng PAI-1 huyt tng tng
ngi c khng insulin. Tng insulin mu lin quan vi gim tiu si huyt
ngi dung np glucose bt thng. Ngi bo ph, m vng bng tng sn xut
PAI-1 kt hp vi khng insulin. bnh nhn T tp 2 vim mn lm tng
fibrinogenPhn tch ha m min dch nhng tn thng t bnh nhn ng
mch vnh cho thy c s mt cn bng h thng tiu si huyt ti ch vi tng
PAI-1 trong m bnh nhn T [86].
C ch l do mt cn bng chc nng gia tPA v PAI-1. Insulin,
proinsulin, VLDL, cc cytokine khc iu ha tng hp v phng thch PAI-
1. PAI-1 tng ng k khi kt hp vi tng insulin, glucose mu v tng acid
bo t do ngi bo ph khng insulin v tiu si huyt gim lin quan
gn vi hi chng chuyn ha [86].
1.2.2.4. Vim
Khi vim, gan sn xut CRP trong p ng sn xut cytokin (IL-6, IL-1,
TNF). Vim lin quan vi bin c tim mch c nghin cu [69]. CRP
c nhy cao (hs-CRP) c s dng nh gi vim trn lm sng [138].
Cc d liu gn y cho thy hs-CRP cao c nguy c T trong tng lai
nh nghin cu CHS (the Cardiovascular Health Study) v IRAS (the Insulin
Resistance Atherosclerosis Study). Trong nghin cu WSCPS (the West of
Scotland Coronary Prevention Study), mu CRP huyt tng 5.245 nam,
trong 127 chuyn t kim sot ng huyt bnh thng sang T trong
sut nghin cu. CRP l tin on quan trng ca s pht trin T trong
phn tch n bin. Trong phn tch a bin, CRP l yu t d bo pht trin
T c lp vi d bo lm sng khc [77].
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16
IL-6 TNF-
GAN
LYMPHO T/MONOCYTE/MACROPHAGE
CRP
KHNG INSULIN CHEMOKINES X VA NG MCH
S 1.3. Tc ng gia vim, khng insulin v x va ng mch [86]
1.2.2.5. Microalbumin niu
Microalbumin niu c xem nh l bin chng ca T do tng
ng huyt lm bin i th pht thn. Microalbumin niu d bo tin
trin bnh thn T. Mt s nghin cu cho thy microalbumin niu xut
hin trc v d bo pht trin T tp 2 v microalbumin niu lin quan
vi d on xu cho nguy c tim mch.
Microalbumin niu l mt trong nhng YTNC tim mch v l mt trong
nhng thnh t c dng xc nh hi chng chuyn ha v microalbumin
niu lin quan vi mc insulin, nhy ca mui, bo ph trung tm, ri lon
lipid mu, ph i tm tht tri v mt khong trng huyt p v m. THA tm
thu l du hiu ca microalbumin niu v tin trin m niu bnh nhn T
tp 2. bnh nhn khng insulin, microalbumin niu c th l du hiu ca
RLCNNM cho thy tng tnh thm ni m v lin quan ti b dy lp ni trung
mc ng mch cnh. Microalbumin niu phn nh albumin qua hng ro ni
mc tng v o lng d dng trn lm sng [86].
M M
VIM
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17
1.2.2.6. Tng homocystein mu (tHcy)
Nhiu nghin cu dch t cho thy tng tHcy lin quan vi bnh XVM,
l YTNC tim mch c lp c bnh nhn T v khng T.
Trong mt nghin cu trn 300 bnh nhn T tp 2, ghi nhn nng
tHcy lin quan mnh m v c lp vi hin din bnh tim mch. Mi mol/l
tng ln ca nng tHcy lin quan bnh tim mch vi t l chnh l 1,45.
Trong nghin cu khc t l chnh mi 5 mol/l tng tHcy trong huyt tng
cho bt k bnh tim mch l 1,38 ngi c dung np glucose bnh thng;
1,55 ngi c RLDN glucose v 2,33 bnh nhn T tp 2 [86]. Nghin
cu ca tc gi Munshi v cng s cng cho thy tHcy tng bnh nhn T
hn so vi nhm chng v hay gp bnh nhn c bnh mch mu ln.
Bng chng tng tHcy mu lin quan ti RLCNNM l phn ng mch
mu, gin mch c lp v l thuc ni mc gim c ngha bnh nhn
T tp 2 ln tui c tng tHcy. Tng tHcy mu lin quan vi albumin niu
v suy thn. Bnh nhn T c microalbumin niu th c tHcy cao hn
bnh nhn c bi tit albumin niu bnh thng. Insulin iu ha chuyn ha
tHcy bng chng c ch lin kt gia tHcy v T [86].
1.2.2.7. Bt thng thnh mch - Dy lp ni trung mc mch mu v
cng thnh mch
Ch s huyt p c chn / cnh tay l phng php thm d khng xm
nhp, hu ch pht hin bnh ng mch ngoi bin di lm sng v c
th cung cp thm thng tin ngoi o lng cc YTNC tim mch.
o b dy lp ni trung mc (IMT) ng mch cnh pht hin s thay
i v cu trc v chc nng xy ra trong thnh mch. IMT tng trong T
tp 2. Mt nghin cu gp IMT ng mch cnh bnh nhn T tp 2 v
ri lon dung np glucose ca G. Brohall v cng s t 23 nghin cu
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18
24.111 i tng; 4.019 T v 1.110 ri lon dung np glucose. Trong 20
ca 21 nghin cu, bnh nhn T c IMT ln hn nhm chng. S khc
nhau trung bnh c tnh trong IMT l 0,13 mm (95% tin cy:0,12-0,14).
Trong 3 ca 9 nghin cu, bnh nhn ri lon dung np glucose c IMT ng
mch cnh cao hn nhm chng l 0,04mm [60].
Cng thnh mch l du hiu khc ca XVM T tp 2. Cng thnh
mch c nh gi bng o p lc mch hoc o vn tc sng mch ng
mch ch. o cng ng mch trong mt s nghin cu v d bo bin c
tim mch trong T tp 2 cho thy cng thnh ng mch lin quan vi
khng insulin, tng quan vi IMT ng mch cnh v RLCNNM [86].
C ch l c s lin kt gia tng IMT ng mch cnh, khng insulin v
tng ng huyt (Nghin cu IRAS -The Insulin Resistance Atherosclerosis
Study). Tng cng thnh mch ngi T c l lin quan glycat ha
collagen ng mch v elastin v tch ly AGEs [86].
1.2.2.8. Tng ng huyt sau n
Tng ng huyt sau n l YTNC tim mch. bnh nhn T, tng
ng huyt sau n lin quan bin chng T giai on mun.
Cc nghin cu dch t cho thy nng glucose 2 gi sau np
glucose l YTNC tim mch c lp v trc tip. Tng ng sau dung np
glucose ng ung s tng nguy c tim mch. Hn na, nng glucose
bnh nhn T sau dung np cng nh sau n lin quan trc tip vi
bnh tim mch, c lp vi ng huyt i v cc YTNC khc.
Nghin cu DECODE nh gi nguy c t vong kt hp tiu ch
glucose lc i ca Hip hi T Hoa K vi tiu ch glucose 2 gi sau
np ca WHO. C s d liu c phn tch t 13 nghin cu on h ca
Chu u, gm 18.048 nam v 7.316 n t 30 tui tr ln. Thi gian theo
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19
di trung bnh 7,3 nm. Bnh nhn T mi chn on bi tiu ch lc i
ca ADA c t l ri ro cht cao hn c ngha so vi ngi c ng
huyt i bnh thng. i vi ngi c glucose i ri lon, t s ri ro
tng nam nhng khng tng n. i vi tiu ch WHO t l gia tng
ng k c nam v n bnh nhn T mi chn on cng nh
ngi RLDN glucose. T vong tng bnh nhn c ng huyt 2 gi sau
n tng. Nng ng huyt i mt mnh khng xc nh tng nguy c
t vong lin quan tng ng huyt. Test dung np glucose bng ng
ung cung cp thm thng tin tin on v cho php pht hin cc i
tng bt thng dung np glucose c nguy c cao nht cho t vong. D
liu ny ng h mnh m quan im tng ng huyt sau n l mt YTNC
ca bnh tim mch [86].
1.3. ENZYME MYELOPEROXIDASE
1.3.1. Ngun gc, cu to v hot ng sinh l ca myeloperoxidase
1.3.1.1. Ngun gc ca myeloperoxidase
Myeloperoxidase (MPO) c tng hp ngay t ty xng, enzyme ny
c cha trong cc ht ban u ca bch cu n nhn v a nhn trung tnh.
MPO khng c phng thch ra ngoi ti khi hot ha bch cu v qu trnh
mt ht ca bch cu [177]. MPO c vai tr trong cc c ch phng th v
p ng min dch [88].
1.3.1.2. Cu to ca myeloperoxidase
MPO c trng lng phn t khong 150 kDa, gm mt cp chui
nng v mt cp chui nh. Tiu n v nng ca chng ni vi nhau bng
lin kt disulfur. Hot tnh peroxidase ca MPO ph thuc vo nhm hem
tng tc vi cu trc protein c 3 lin kt ng ha tr v 8 lin kt
hydrogen [110].
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20
Hnh 1.1. Cu trc enzyme myeloperoxidase [73]
1.3.1.3. Hot ng sinh l ca myeloperoxidase
MPO to ra cht oxy ha c vai tr trong phn ng oxy ha thnh
mch [74]. MPO xc tc bin i gc tyrosyl, chlorination sinh ra tyrosine
peroxide v oxy ha lipoprotein huyt tng [75]. MPO to ra
hypochlorous acid (HOCl) t phn ng hydrogen peroxide (H2O2) v ion
clo (Cl-) [76]. HOCl l cht oxy ha mnh c tc dng chng khun. Tuy
nhin, vic sn xut HOCl ko di v thng xuyn gy tn thng m v
khi u v tin trin bnh mch mu [75], [134]. MPO l mt enzyme
mang in tch dng mnh nn d dng gn vo mng sinh hc mang in
tch m, c bit ch vim nh glycosaminoglycan ca cht nn ngoi
bo, lipoprotein LDL [176].
Hnh 1.2. Phn ng to ra hypochlorite
S clo ha bi HOCl: MPO l enzyme duy nht ngi sinh ra HOCl
[120]. HOCl l tc nhn oxy ha mnh c kh nng oxy ha phn t sinh hc
Dit khun
i thc bo
Tn thng
vt ch
../../TLTK%20%20T%20NCS.%20CHI/TLTK%20tu%2036-52/41.%20Zhang.Leukocyte.doc
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21
nh carbohydrate, acid nucleic, lin kt peptide, amino acid. HOCl oxy ha
nhm sulfhydryl v thioether ca protein, clo ha nhm amino thnh
chloramine, chuyn L-tyrosine thnh 3- chlorotyrosine, chuyn cholesterol
thnh phc hp clo ha [120], [144].
Gc tyrosine: MPO cng hot ng nh peroxidase kinh in v khong
5% ca hydrogen peroxide tiu th bi enzyme to ra gc tyrosyl. Chuyn l-
tyrosine thnh gc tyrosine c s tham gia ca cc cht oxy ha nh peroxide
ha lipid LDL. Gc tyrosine c th thc y oxy ha lipid v protein. C 3-
nitro v 3- chlorotyrosine tng trong mng XVM [103].
Mu phn ng nitrogen: MPO c xem nh mt oxy ha NO quan
trng trong mch mu, c th oxy ha nitrite (NO2) thnh dng phn ng.
MPO dng NO2- phn ly, thnh cht trung gian clo ha v nitrate ha [120].
1.3.1.4. Cc bnh l lm tng myeloperoxidase
Hot ng ca MPO lin quan n qu trnh vim. Mc MPO tng
bnh nhn bnh ng mch vnh. Qu trnh oxy ha gii phng MPO cn gp
bnh ri lon thoi ha thn kinh, ung th, bnh l ng h hp, vim
khp dng thp, tn thng thn v x va ng mch.
D liu gn y cho thy s lin kt gia tng nng MPO v pht
trin bnh i tho ng lin quan n enzyme vai tr l cht xc tc cho
phn ng oxy ha thnh mch mu. MPO tham gia iu chnh nitric oxide
l phn t c vai tr quan trng trong trong sinh l bnh [88].
1.3.2. Vai tr ca myeloperoxidase trong x va ng mch
Thut ng stress oxy ha c dng m t tnh trng tn thng oxy
ha t bo, t chc hoc c quan gy ra bi cc sn phm oxy ha phn ng
[95], [105], [120]. Nu stress oxy ha mc nh th cc phn t sinh hc
b tn thng c th sa cha hoc thay th bng cch gia tng kh nng
chng oxy ha nhng nu mc trm trng v ko di c th gy ra tn
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thng hoc cht t bo, bao gm hoi t v cht theo chng trnh. Cc
cytokine gia tng sau tn thng ni mc, stress bin dng v ph v c hc
iu ha to ROS. Bnh hc ca XVM l tng ROS [120].
Superoxide (O2-), hydrogen peroxide (H2O2), hydroxyl (
.OH), oxidize
nitric (NO2-), peroxynitrite (OONO-), hypochlorous acid (HOCl) l nhng gc
t do tham gia qu trnh XVM [100].
MPO c kh nng to ROS nh HOCl, chloramin, gc v NO2. Cc cht
ny oxy ha protein, lipid v cc thnh phn chng oxy ha ca LDL [148].
HOCl bin i protein c tm thy trong tn thng x va v v th MPO
lin quan vi s oxy ha LDL qua trung gian i thc bo [133], [144].
1.3.2.1. Lin kt myeloperoxidase v bnh l tim mch
Ngy nay vim v stress oxy ha to cc gc t do gp phn vo pht
trin v tin trin ca qu trnh XVM. MPO l mt phn t tin vim c lin
quan trong vic thc y v lan rng ca XVM. MPO c tit ra t bch
cu ti cc v tr vim s chuyn LDL vo mu x va, to ra nhiu ROS v
lm gim NO sn c, qua gp phn lm RLCNNM. S tch ly MPO trong
cc mng x va gy nn s khng n nh ca cc mng x va ny dn n
bong mng x va v sau cng nh hnh thnh cc cc nghn mch [68].
Nhiu bng chng cho thy MPO ng mt vai tr trong XVM nh
nghin cu on h ca Clair L.Heslop v cng s trn 885 bnh nhn theo
di 13 nm t vong do mch vnh cho thy mc MPO cao th nguy c gp
i gy t vong tim mch. o lng c MPO v CRP cung cp thm li ch
cho d bo nguy c hn l ch CRP mt mnh [99]. Nhng ngi c MPO
tng c th c bnh mch vnh trong tng lai c chng minh. MPO
tch t trong thnh ng mch v tng v tr tn thng nhng bnh nhn
t t do tim. MPO cao d on sm nguy c tim mch tng lai v c
lp nhng bnh nhn hi chng mch vnh cp trc 24 thng. Tri li
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nhng ngi thiu MPO hon ton hoc gn hon ton do khim khuyt
bm sinh (tn xut khong 1/2000-1/5000 Hoa K v Chu u, 1/55000
Nht) th t c kh nng mc bnh mch vnh [133], [144].
Hnh 1.3. Tin trnh x va ng mch lin quan MPO [133]
Cc nghin cu lm sng cho thy o nng MPO c gi tr trong
nh gi tnh trng bnh l ca nhng bnh nhn au ngc, cc trng hp
nghi ng c hi chng mch vnh cp v suy tim. MPO l yu t c lp gip
nh gi nguy c khng ph thuc vo cht ch im sinh hc khc nh men
tim CK-MB (Creatine kinase-myocardial band) hay CRP. o nng MPO
kt hp vi peptid li niu loi B (BNP-B-type natriuretic peptide) c gi tr
tin lng trn nhng bnh nhn suy tim. Nghin cu cho thy nhng trng
hp c tng c MPO v BNP th t l sng cn thp nht. o MPO cung cp
thm thng tin tin lng trn nhng bnh nhn c hi chng mch vnh cp.
Brennan v cng s nghin cu cc bnh nhn t t v nguyn nhn
tim mch, nng MPO bch cu tng nhng mng x va l th phm
lm mng x va b v hoc nt. Nghin cu cho thy mi lin kt c ch
gia MPO vi c vim ln bnh tim mch. Cc tc gi nh gi vai tr
ca nng MPO huyt tng trong vic d on cc bin c tim mch v
Tn thng c tim Hot ha Protease Ti to tm tht bt li
Suy tim
Mng va ban u/tin trin Gim xc tc NO
To lipid hot ng sinh hc Ha hng ng bch cu
To LDL gy x va
To HLD ri lon chc nng
Mng va tn thng Hot ha yu t m
Hot ha Protease
T bo ni mc cht theo chng trnh
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nh gi tng quan gia nng MPO v cc bin c tim mch chnh nh
nhi mu c tim (NMCT), nhu cu ti thng mch vnh hay t vong trc
mt (30 ngy) v lu di (6 thng) 604 bnh nhn n phng cp cu v
au ngc. Nghin cu cho thy nng MPO huyt tng d on NMCT
ngay c nhng ngi lc u c troponin T m tnh. Nng MPO cng
d on t l b cc bin c tim mch trc mt v lu di (p
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di lp ni mc to LDL l mc tiu chnh cho s oxy ha bi tin cht oxy
ha c sn xut bi t bo thnh ng mch. MPO l mt protein mang
in tch dng mnh v c th ni kt t bo ni mc, bch cu v LDL. S
kt hp MPO vi LDL lm tng oxy ha ca lipoprotein ny. MPO sinh ra
ROS, chng oxy ha protein, lipid v hp cht chng oxy ha ca LDL.
Nhiu sn phm oxy ha ban u khng n nh v hot ng nh l cht
trung gian thc y hn na to LDLoxh v c l dn n lin kt ngang v
khi kt tp. Tyrosine sau khi bin i cn li 3-nitrotyrosine v 3-
chlorotyrosine l nhng cht c trng nht ca cht oxy ha n nh ny.
MPO cng lin quan ti chuyn i tyrosin thnh 3-nitrotyrosin t cc dng
phn ng nitrogen bn cnh nhng c ch khc cng to 3-nitrotyrosin nh
peroxynitrite (sn phm phn ng ca nitric oxide v superoxide). Tri vi 3-
nitrotyrosine, 3-chlorotyrosine c to ra duy nht bi MPO v c l l cht
ch im phn t duy nht cho s oxy ha cht xc tc MPO [148].
Hazen, Heinecke v cc cng s bo co rng 3-chlorotyrosine cao
gp 6 ln bnh nhn c tn thng XVM so vi m ng mch ch bnh
thng. Hn na, nng 3-chlorotyrosine trong LDL lin quan t ni mc
x va cao gp 30 ln LDL trong huyt tng. Nhng d liu ny a ra gi
thuyt mnh m rng MPO lin quan trong vic bin i LDLoxh ni mc
mch mu, kt qu lm chuyn LDL vo lp x va [144], [148].
Myeloperoxidase lm suy gim chc nng ca HDL
Bn cnh vai tr chnh l a cholesterol v vn chuyn ngc cholesterol,
HDL cn c vai tr chng vim v chng oxy ha. Mc d c ch chnh xc
khng c hiu y , mt vi apolipoprotein v enzyme lin quan ti ht nh
HDL c kh nng cha ng cc cht chng oxy ha. Sau khi hp thu bi HDL,
cc sn phm oxy ha ny c cc enzyme lin quan HDL nh cht kt dnh
tiu cu acetylhydrolase v paraoxonase thy phn hoc vn cn lin kt vi
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HDL v cui cng b loi ra khi tun hon sau khi gan hp thu HDL. Hot ng
khng vim ca HDL gn lin hot ng chng oxy ha ca n, bi v cc lipid
b oxy ha thnh cht tin vim mnh v gy vim ng mch. HDL lm gim
gn kt bch cu ln t bo ni mc v c ch bm dnh ca bch cu ti cc t
bo ny v a cc t bo vim vo trong ni mc.
Trong cc bnh chuyn ha lin quan tc XVM, cc ht HDL c th
tr nn khim khuyt chc nng. Cc ht HDL ri lon chc nng mt i c
tnh chng x va v thc y tc dng tin vim. MPO c lin quan ti ri
lon chc nng to hnh ca HDL. Apolipoprotein A-I (apoA-I) l mt mc
tiu u tin cho qu trnh oxy ha xc tc MPO, c chng minh bng cch
cho gp 100 c 3-nitrotyrosine v 3-chlorotyrosine vo apoA-I thu li t HDL
tun hon so snh protein khc trong tun hon. Hn na s thm vo ca cc
bin i oxy ha trong apoA-I lin quan t mng XVM ngi thm ch cn
cao hn. Hm lng 3-nitrotyrosine v 3-chlorotyrosine ca HDL cao lin
quan vn chuyn ngc cholesterol ca HDL b gim. S lin quan mnh m
gia s bin th apoA-I v t l ca bnh tim mch c quan st, hm
lng apoA-I 3-chlorotyrosine trong tam phn v cao nht nhiu kh nng b
bnh tim mch gp 16 ln khi so snh vi ngi c hm lng apoA-I 3-
chlorotyrosine trong tam phn v thp nht [134]. Mc tiu MPO la chn
apoA-I c gii thch l do apoA-I c v tr gn kt c hiu vi MPO [148].
HDL b bin i do MPO cng lm tng i lc lin kt HDL vi
MPO hn na, dn n vng ln qun ca s bin i HDL ph thuc
MPO ni vim mn. Nitrotyrosine v chlorotyrosine l du ch im
phn t ca MPO lin quan trong vic bin i oxy ha ca HDL lm
HDL ri lon chc nng [144], [148].
Myeloperoxidase lm gim kh nng sinh hc ca nitric oxide (NO)
NO c sn xut bi eNOS. NO l cht gin mch mnh v c vai
tr then cht trong iu ha mch mu. NO cn ngn chn s kt ni cc
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t bo trong h tun hon ti lp ni mc v c ch s pht trin ca cc
t bo c trn vo thnh mch mu. Do , s sn xut khng y v
hoc tng thu dn ca NO lm suy yu chc nng mch mu v thc y
XVM [167]. MPO c vai tr iu ha NO c cp nhiu
nghin cu [88].
Mt s c ch ca MPO lm gim tnh sinh kh dng ca NO [148]:
- NO ng vai tr l cht nn cho peroxidase v MPO xc tc.
- NO b tng thu dn t cc cht phn ng do MPO to ra dn n lm
gim kh nng sinh hc ca NO.
- HOCl c th phn ng vi nguyn t nitrogen ca NOS l cht nn
arginin sn xut cc dng chlorinat arginin chng c ch ng dng ca
NOS lm gin mch ph thuc ni mc ng mch suy gim.
- HOCl tc dng tho cp i eNOS mnh do vic to NO t eNOS
gim v NOS tr li to enzyme sn xut superoxide.
Hnh 1.4. Tc ng ca HOCl ln tho cp NOS to gc t do superoxide [88]
Tho cp eNOS xy ra khi tetrahydrobiopterin ca L-arginine gim
hoc b bin i. eNOS chuyn to gc superoxide lm sn xut NO gim.
S c ch
cht nn
Nitrat ha protein Oxy ha lipid Oxy ha protein
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Nh vy, MPO bng tin trnh xc tc cng nh khng xc tc lm
suy yu NO thnh mch. S ng thun ny c quan st trong
nghin cu mi lin quan mnh m gia nng MPO trong huyt tng
v gin mch ng mch cnh tay c ngha sau khi iu chnh cc YTNC
tim mch v CRP. Trong nghin cu ca Baldus v cng s, s phng
thch MPO t mch mu di ni mc khi truyn heparin lm tng gin
mch dng chy cnh tay v tng dng mu cnh tay do acetylcholine kt
qu lm ci thin chc nng mch mu ph thuc lp ni [148],[170].
Dng mu
Lp o trong
T bo c trn
Vn chuyn ngc
cholesterol
Nt mng bm
Vt m
TB bt
Hnh 1.5. Tc dng bt li ca myeloperoxidase [148]
LDL vo ni mc thnh LDLoxh. Bch cu vo ni mc thnh i thc
bo (TB). TB hp thu LDLoxh thnh t bo bt. MPO t TB phng thch
xc tc to ROS. ROS to t MPO (MDRS) s dng clorua, thiocyanate hoc
NO lm cht nn v H2O2 lm ng cht nn. Thu dn NO lm gin mch b
suy yu. MPO thc y XVM bng cch bin LDL thnh LDLoxh, thc y
to HDLoxh lm ri lon chc nng HDL, mt n nh cc mng x va.
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Myeloperoxidase lm tn thng mng x va ng mch
Cc mng x va ng mch vnh b vim d b tn thng b v v
xi mn c th gy ra cn au tht ngc khng n nh. Mng x va bt
n v v l tin trnh ch yu trong qu trnh bnh tim mch cp [62].
Rossi v cng s tm thy t l mng x va khng n nh cao bnh
nhn NMCT cp. MPO gp phn lm bt n mng x va bng cch hot
ha men tiu protein (metalloproteinase) t lm suy yu v bc mng
x va. iu ny c mt vi nghin cu cho thy mi lin quan
thun gia MPO v t vong do bnh tim mch bnh nhn bnh mch
vnh cp [93], [148].
Hnh 1.6. C ch ca MPO trong x va ng mch [144]
Cc bng chng v vai tr ca MPO trong mng x va khng n nh
c th hin t nhng nghin cu sinh bnh hc. Mng x va tn thng
hot ha bch cu dn n phng thch MPO. Malle v cng s quan st s
bin mu ca MPO v protein bin i hypochlororite trong tn thng
XVM [148]. Sugiyama v ng s cng chng minh trong mng x va
Gii phng cc mu oxy phn ng (ROS)
Bin i LDL hnh
thnh dng tin x va
i thc bo thu nhn
LDL-C trung gian
Gim chc nng vn
chuyn ngc ca HDL
Tiu th xc tc NO
Ri lon chc nng ni mc
T bo ni mc cht
theo chng trnh
Hot ha men tiu
protein
Kt dnh tiu cu
thun li
Tng phn ng mch mu
Mng bm khng n nh
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ca bnh nhn t t cc ch v, xi mn v li lipid th giu MPO, trong khi
cc vt m cha ng t hoc khng c MPO [144]. Ph hp vi quan st ny
cc nh nghin cu tm thy nng tp trung ca protein bin i bi
HOCl cao trong mng x va b xi mn hoc b v mng khi so snh vi
mng n nh. Tm li, cc d liu cung cp bng chng mnh m rng MPO
tham gia vo chuyn XVM giai on cui vo bin c tim mch cp [148].
1.3.2.3. Vai tr ca myeloperoxidase trong i tho ng
Ri lon chc nng ni mc l yu t gp phn chnh ti bnh sinh ca
bin chng mch mu T. Nng glucose tng cao v ko di trong T
l yu t chnh dn n hng lot ri lon chuyn ha v c th gy stress oxy
ha to ra ROS [107]. ROS nh superoxide v hydrogen peroxide (H2O2) l
phn t quan trng trong sinh bnh hc ca bin chng mch mu T bao
gm RLCNNM. Cht oxy ho NAD(P)H, cht oxy ha khng t bch cu,
c chng minh l ngun gc chnh ca ROS trong mch mu T [176].
Bch cu ng vai tr quan trng trong sinh bnh hc ca bin chng
mch mu T. Ngoi ra, nhim trng ti din l mt trong nhng c im
lm sng chnh ca bnh nhn T v vim do nhim trng s lm nng
thm tn thng mch mu T.
MPO l mt hem protein phng thch t bch cu, ng vai tr quan trng
trong tn thng mch mu gin tip phn ng khi b kch thch trong bnh
mch mu vim nh XVM. MPO bin i LDL. Mc MPO cao, MPO phng
thch 3-chlorotyrosine v HOCl-bin i LDL c pht hin tn thng
XVM ngi. MPO c vai tr trong bnh ng mch vnh v hi chng
mch vnh cp c ghi nhn trong nghin cu lm sng.
Ngy nay, thy rng MPO gy RLCNNM ph thuc H2O2. Kh nng sinh
ha NO gim lm RLCNNM bin i bi h thng (MPO/HOCl/chloramines).
Trong nghin cu Baldus v cng s cho thy MPO l protein vn chuyn t
bo. Khc vi H2O2 tit t bch cu c thi gian bn hy ngn, MPO gn kt
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mch mu c th tn ti trong thnh mch mt thi gian c ngha. MPO c
th dng H2O2 phng thch t bch cu v khng t bch cu tit ra. MPO c
th dng cht oxy ha H2O2 to ra t ng huyt cao khng t ngun gc
bch cu sn xut HOCl v dng chlorinate. Quan trng hn, cc dng
chlorinate v HOCl c ngun gc t MPO lm tng ROS gy ra tn thng
bng suy yu gin mch ph thuc ni mc.
S gia tng ROS nh H2O2 trong mch mu T v s hot ha, kt
dnh v s thm nhp bch cu vo thnh mch mu l mt thnh phn then
cht trong pht trin bin chng T [176].
Hnh 1.7. C ch MPO tng tc vi gc t do chn lc nh hng bt li
trong lp ni mc [88]
Nhiu c ch to ra ROS do tng glucose mu trong T nh c ch t
ng oxy ha, s hnh thnh cc AGEs v kch hot con ng polyol c th
VIM
NI MC
T BO C TRN MCH MU
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gy stress oxy ha [163]. Bn cnh vic tng sn xut ROS ca ty th
trong iu kin glucose mu tng l nguyn nhn chnh gy bin chng lm
sng lin quan ti T v bo ph. Mt s nghin cu chng minh s gia
tng cc du ch im ca cc gc t do gy tn thng mch mu th hin s
suy yu trong phng th chng oxy ha ca chng [107].
1.4. CC PHNG TIN THM D TN THNG X VA NG
MCH CNH
Kho st ng mch cnh ngoi s bng hnh nh khng th thiu nhm
chn on bnh l x va ng mch cnh.
1.4.1. Siu m
1.4.1.1. Siu m ng mch cnh qua da
Kho st siu m h thng mch mu ng mch cnh cn hai k thut:
Siu m B- mode cho hnh nh mch mu v tn thng thnh mch vi u
d tn s cao ( 7,5 MHz); Siu m Doppler phn tch cc ch s huyt ng
hc ni mch.
B dy lp ni trung mc
Siu m B-mode miu t lp ni-trung mc nh cu trc hai ng.
Hnh 1.8. B dy lp ni trung mc ng mch cnh chung bn tri
dy 2,8mm [94]
o IMT ng mch cnh c s dng rng ri bao gm: Kim tra
yu t nguy c mi xut hin. nh gi hiu qu dng thuc iu tr cc
http://radiographics.rsna.org/content/25/6/1561/F15.expansion.html
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33
yu t nguy c c th thay i ln tin trnh thay i thnh ng mch giai
on sm [64].
Nhc im: Thit b khng c chun ha, khc nhau v thc hin
cc trung tm khc nhau. Nhng kh khn khi o IMT l cht lng hnh nh
km, my khng ph hp, lch v gii phu ca bnh nhn kh nh c c
ngn, ch phn nhnh ng mch qu cao, mch mu quanh co hoc khng
nm phng c do bnh h hp hoc bnh tim.
Hnh thi hc mng x va
Dng B-mode nh gi. Mng ng nht dng si (mm) hoc calci
ha (cng) v c cu trc bn trong nh nhau vi b mt nhn. Mng khng
ng nht v mng lot khng n nh hoc d vn c kh nng thuyn tc.
Nhng mng c triu chng ny c calci thp hn nhng s lng xut huyt
trong mng v lipid ln hn v chng gim m. Mng bm gim m c kh
nng nhiu triu chng hn mng tng m [94].
Hnh 1.9. Hnh nh mng x va ng nht [94]
1.4.1.2. Siu m ni mch (Intravascular ultrsound, IVUS)
Nissen v cs bo co siu m ni mch vo nm 1991 [101]. IVUS dng
u d qua da lung vo lng mch ti v tr kho st bng h thng thng
lung rt nh v dy dn mng di hng dn cht cn quang.
http://radiographics.rsna.org/content/25/6/1561/F16.expansion.html
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Hn ch v u im ca IVUS
y l mt k thut xm nhp, dng u d n v nhiu loi vi tn s
cao, chi ph cao nn s dng gii hn ch trung tm chuyn bit. Nguy c c
th xy ra khi thao tc thng lung bng tay v bt buc i qua tn thng
hp. Li ch cn chng minh l cn thit hn nguy c lin quan.
Vi s phn gii cao, IVUS tt hn siu m ngoi da chng minh dy
ni mc v mng bm; kho st c tnh ca mng cng tt hn nh phn
bit kiu mng bm l mng hoi t hay mng x [173]. IVUS dng
nh gi tn thng x va mch, phnh bc tch v ngay c cu trc gn
thnh mch.
Hnh 1.10. Cc lp ca thnh ng mch trong qua IVUS [173]
(a) lp ni mc, (b) lp trung mc,(c) lp ngoi mc, (P) mng bm.
1.4.2. Chp mch cng hng t (Magnetic resonance angiography, MRA)
u im v hn ch
MRA l k thut khng xm nhp v bnh nhn khng b phi nhim
cht phng x hoc cht cn quang iod, cho hnh nh 3 chiu ton b ng
mch cnh hoc ng mch t sng thn nn, hu ch xc nh hp
nng ng mch, tc mch v dng bng h.
MRA dng t trng mnh v sng radio to ra hnh nh nn d b
nh hng nhng iu kin lm cn tr dng mu phn lp. Khng chnh
Downloads/Documents/chuyende%20NCS/TLTK_CD3/51.Wilhelm_Schberle-Ultrasonography_in_Vascular_Diagnosis__A_Therapy-Oriented_Textbook_and_Atlas,_Second_Edition-Springer(2011).pdf
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xc, cho nhiu nh nhng ngi mang kim loi. nh hng ca chuyn
ng. Dng mu chy chm v hn lon s mt tn hiu nn khng phn bit
tc hon ton hay gn tc [127].
Hnh 1.11. Chp MRA ca ng mch cnh trong [127]
A: ng mch cnh trong mt tn hiu hon ton (mi tn); B: ng
mch cnh bnh thng. C: ng mch cnh trong hp nng ch xut pht (mi
tn), mt mng x va c lot pha xa on hp (u mi tn).
1.4.3. Chp mch ct lp vi tnh (Computed tomographic angiography, CTA)
Ngy nay vi k thut v x l hnh nh nhanh, CTA tr thnh cng c
mnh chn on hnh nh mch mu thn kinh nht l trong tnh hung cp
cu i hi mt k thut hnh nh nhanh, thit thc gii p nhng cu hi
sng cn trn lm sng cho quyt nh iu tr r rng [126].
Hn ch v u im ca CTA
Khng cung cp cc d liu nh vn tc, hng chy. Vng vi ha
nng chm tia b cng i, gim chnh xc khi dng hnh. Nguy c c cho
thn hoc phn ng d ng do cht phng x v thuc cn quang [128].
CTA kh thi cho hnh nh ng mch cnh x va, kho st tun hon
ng mch cnh d dng v nhanh. CTA thun tin v nhanh hn DSA. CTA
o ng knh lng mch, b dy mng bm rt tt, c nhy 96-100% khi
dng siu m ni mch tham kho. Calci ha trong mng bm v cu trc
Downloads/Documents/chuyende%20NCS/TLTK_CD3/56.CTA.S45.full.pdf
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36
gii phu mch mu d dng xc nh v tr v nhn dng mng XVM. CTA
gip theo di hnh nh y cho nghin cu tin cu, m t tt c tn
thng hp r rng tng t chp DSA. Gii phu mch mu phc tp khng
cn tr cht lng CTA v ti dng hnh c th to trong bt k hnh chiu
nu khng c xo nh t cu trc xung quanh [53].
Anderson v cng s chng minh chp n lt ct c nhy 89%,
c hiu 91% v chnh xc l 90% pht hin hp M cnh trn 50%
cn Josephson v cng s cho thy vi chp a lt ct cho nhy cao
(100%) nh gi hp ng mch cnh trn 70%.
Hnh 1.12. Hnh chp CTA ng mch cnh [53]
Vi ha ng mch cnh hai bn (mi tn); Hp ng mch cnh bn
phi (u mi tn)
1.4.4. Chp mch mu s ha xa nn (Digital subtraction angiography, DSA)
DSA l tiu chun vng chn on hnh nh mch mu.
Hn ch v u im ca chp mch mu
Chp DSA l k thut xm nhp, i hi c kinh nghim v iu kin l
tng, thc v kh nng hp tc ca ngi bnh cng nh cht lng nh.
Bnh nhn c theo di du hiu sinh tn v tnh trng thn kinh trong sut
qu trnh kho st v sau chp 12-24 gi. ng vo t ng mch i c
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37
nguy c bin chng ti ch thp hn cc ng vo ng mch nch, cnh
chung. Chi ph v cc nguy c lin quan nh nhi mu no do thuyn tc
ng mch cnh v cht cn quang [117] l tr ngi ca chp DSA. Bin
chng t qu, xut hin
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38
ph, suy thn hoc mang kim loi m v mt k thut CTA hoc MRA khng
y hoc khng th chp ng mch, khi nghin cu hnh nh khng xm
nhp cho kt qu mu thun nhau. DSA c s dng nh th thut ti thng
mch mu iu tr kt hp trin khai t stent [61].
1.5. CC NGHIN CU V MYELOPEROXIDASE LIN QUAN N
TI
1.5.1. Nghin cu myeloperoxidase trong bnh l tim mch
Cc nghin cu dch t cho thy MPO lin quan vi bnh tim mch v
cc du ch im XVM bnh nhn XVM v bnh nhn au ngc cp
[148]. Nghin cu ct ngang ca Zhang v cng s (2001) v mi lin quan
gia MPO vi bnh ng mch vnh (MV) 158 bnh nhn c bnh MV
v 175 ngi chng cho thy nhm bnh MV c MPO cao hn so vi nhm
chng v MPO lin quan n nguy c tng bnh MV [177]. Nghin cu ca
Duzguncinar v cng s cho thy MPO tng bnh nhn bnh MV v
tng quan vi mc trm trng ca XVM. Trong nghin cu EPIC
(European prospective investigation into cancer and nutrition) v s lin quan
gia MV v MPO 1.138 bnh nhn khe mnh sau c bnh MV
trong 8 nm theo di so snh vi nhm chng 2.237 ngi, Meuvese v cng
s ghi nhn nng MPO cao nhm c bnh MV, MPO lin quan vi
nguy c pht trin bnh MV trong tng lai nhng ngi khe mnh, c
lp vi cc YTNC truyn thng [71], [125].
Ndrepepa (2008) nghin cu ct ngang gm 680 bnh nhn bnh MV
vi 382 bnh nhn c bnh MV n nh v 194 chng vi chp mch vnh
bnh thng, nng MPO bnh nhn bnh tim mch cao hn so vi nhm
chng. Hn na, nng MPO lin quan vi s hin din bnh MV.
Mocatta v cng s nghin cu 5 nm tt c nguyn nhn t vong 512 bnh
nhn vi NMCT thy rng bnh nhn c MPO tng trn mc trung bnh th
nguy c tng gp 2 ln tt c cc nguyn nhn gy t vong so vi bnh nhn
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39
c MPO di mc trung bnh. Tc gi Dilshad Ahmed Khan v cng s cng
cho kt qu tng t [108]. Nng MPO cao cn l yu t tin on c lp
t vong trong bnh vin bnh nhn NMCT c ST chnh c chong tim
[111]. Baldus v cng s nghin cu CAPTURE gm 1.090 bnh nhn hi
chng mch vnh cp trong 6 thng theo di gi tr tin on ca MPO cho t
vong v NMCT cp. Bnh nhn c MPO tng th nguy c ti nhi mu hoc
t vong gp 2,25 ln. Mc thay i MPO khng tng ng vi Troponin T
[59]. Julia Searle cng cho rng MPO hu ch nh gi bnh mch vnh
cp bnh nhn ban u c troponin m tnh [149]. Marit Granr v cng s
cho thy o MPO thm ngoi troponin s gip chn on chnh xc bnh
mch vnh cp [92]. Nghin cu on h ca Esporcatte R v cng s 140
bnh nhn, c 49 (35%) c chn on b hi chng mch vnh cp, trong
13 bnh nhn (9,3%) c chn on NMCT khng c ST cao. im ct
MPO tt nht cho NMCT c xc nh l >100 pmol/l. Trong phn tch a
bin, MPO c chng minh l bin c lp duy nht chn on NMCT
cp vi t s nguy c (OR) 8,04 (p = 0,048). Nh vy bnh nhn cn au
ngc cp v khng c ST chnh, MPO cao l mt cng c quan trng tin
on yu t cho nhp vin [80]. W.H. Wilson Tang v cng s (2011) nghin
cu 1.895 bnh nhn c bnh MV theo di 3 nm cc bin c tim mch bt
li chnh (major adverse cardiovascular events -MACE) nh t vong, NMCT
cp, t qu th nhng bnh nhn c MPO>322pmol/l s tng nguy c b
MACE trong tng lai [158].
Mt nghin cu trong nc ca tc gi Nguyn Thanh nh v Hunh
Vn Minh nm 2011 v nng MPO huyt tng v mi lin quan vi mc
nng bnh nhn NMCT cp cho thy nng MPO tng nhm NMCT
cp hn so vi nhm chng (p = 0,01) v c s tng quan thun gia nng
MPO huyt tng vi mc nng ca bnh [16].
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40
1.5.2. Nghin cu myeloperoxidase trong bnh l i tho ng
Wiersma JJ v cng s cho rng T tp 2 c lin kt vi RLCNNM
v XVM gia tng nhanh khi nghin cu so snh MPO huyt tng bnh
nhn T vi khng T c cn au tht ngc n nh v nh t 440 bnh
nhn c tuyn t cc phng khm tim mch ngoi tr, vi 268 bnh nhn
T tp 2 v 172 bnh nhn khng c T tp 2. Phn tch hi quy tuyn
tnh a bin iu chnh cho cc yu t nhiu. Kt qu: Nng MPO cao
bnh nhn T (trung bnh 141 pmol/l; khong t phn v 115-171 pmol/l)
hn so vi nhng bnh nhn khng T (trung bnh, 126 pmol/l; khong t
phn v 105-167 pmol/l) (p = 0,01). Nghin cu ny kt lun rng T tp 2
lin quan vi tng nh MPO, c lp ca cc bin khc trn lm sng. Mi
lin quan ny th hin tin trnh XVM bnh nhn T [172].
Gim HDL v tng stress oxy ha l c trng ca T tp 2. MPO l
mt enzyme oxy ha mt phn lin kt vi HDL v gy ri lon chc nng
HDL, MPO l yu t nguy c c lp cho bnh tim mch. Paraoxonase-1 l
mt enzyme HDL-lin kt bo v chng li bnh tim mch v gim bnh
T. Jornayvaz FR v cng s (2009) nghin cu v nng MPO trong
huyt tng v paraoxonase-1 bnh nhn T tp 2 v bnh nhn khng c
T, c v khng c bnh tim mch. Kt qu: Nng MPO huyt tng
tng ng k cc nhm bnh nhn c v khng c T c bnh mch vnh.
Phn tch a bin cho thy MPO huyt tng l mt yu t nguy c c lp
thc y ri lon chc nng HDL v lm tng nguy c tim mch [103].
Trong nghin cu ca Leonard P. Vander Zwan v cng s (2009) ghi
nhn nng MPO l du ch im lin quan n qu trnh vim nhim v
stress oxy ha khi o nng MPO 230 bnh nhn c nng glucose bnh
thng v 386 bnh nhn c glucose bt thng cho thy bnh nhn c
chuyn ha glucose mu bt thng th nng MPO tng [166].
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41
Fabio R Tavora v cng s (2009) nghin cu 61 bnh nhn v mng x
va cp, 15 bnh nhn v cp, 15 trng hp v c t chc, 31 va ng
mch c bao mng v 28 x va ng mch t 72 bnh nhn t t do bnh
ng mch vnh bng k thut sinh ha m min dch v sinh ha m. Kt
qu t bo dng tnh vi MPO hin din nhiu hn tc mch hon ton so
khng hon ton gy v mng x va (p=0,006) v s lng nhiu hn
bnh nhn T so vi khng T (p=0,002) [160].
Elena Moldoveanu v cng s nghin cu mi lin quan gia
lipoprotein-phospholipase 2, MPO v paraxonase nhng enzyme ny lin
quan ti tin trin ri lon chc nng ni mc bnh nhn T tp 2 t 100
bnh nhn T: 50 khng c bnh mch vnh (nhm 1); 50 c bnh mch
vnh (nhm 2) v 46 ngi chng khe mnh. Kt qu cho thy lipoprotein-
phospholipase 2 cao nhm 2 hn nhm 1 v nhm chng. Paraxonase
nhm 1 thp hn nhm chng v thp nht nhm 2. MPO cao bnh nhn
T hn nhm chng [131].
Heilman K v cng s xem nhng thay i chc nng, cu trc ca
ng mch vi du ch im sinh ha mi ca x va mch l MPO t 30
bnh nhn T, thi gian mc bnh 5,43,4 nm c xt nghim MPO
v o IMT ng mch cnh so vi 30 ngi chng. Kt qu bnh T c
MPO tng (p=0,006), IMT tng (p=0,005) so vi nhm chng [97].
Cho n nay, ti Vit Nam cc nghin cu v MPO cn rt t. Chng ti
cha tm thy nghin cu no trong nc cp n enzyme ny bnh nhn
T ni chung cng nh bnh nhn T tp 2 ni ring.
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42
Chng 2
I TNG V PHNG PHP NGHIN CU
2.1. I TNG NGHIN CU
i tng nghin cu gm nhng bnh nhn T tp 2 ang iu tr ti
khoa ni Bnh vin a khoa Trung tm Tin Giang v c nhm tham chiu l
nhng ngi khe mnh khng b T.
2.1.1. Nhm bnh i tho ng tp 2
2.1.1.1. Tiu chun chn on i tho ng
Chng ti dng tiu chun chn on ca ADA nm 2010 [46], [47].
T c chn on khi c t nht 1 trong 4 tiu chun sau:
+ Nng HbA1C 6,5% v/hoc
+ Nng glucose huyt tng lc i (t nht sau 8 gi khng n) 7
mmol/L (126mg/dL), v/ hoc
+ Nng glucose huyt tng 2 gi sau lm nghim php dung np
glucose 11,1 mmol/L (200mg/dL), v/hoc
+ Nng glucose huyt tng bt k 11,1mmol/L (200mg/dL ) km
triu chng lm sng c in nh tiu nhiu, ung nhiu, st cn.
Chn on c xc nh khi thc hin li xt nghim ln th hai
nhng ngi c ng huyt bt thng (HbA1C, glucose huyt tng lc
i, glucose huyt tng sau 2 gi) vn t tiu chun chn on.
Trong nghin cu ny, chng ti da vo 2 tiu chun (glucose huyt
tng i hoc glucose huyt tng bt k) trong 4 tiu chun trn.
2.1.1.2. Tiu chun chn on i tho ng tp 2
- Chn on T tp 2 da theo tiu chun ca Lin on T th gii
v T chc Y t Th gii 2005 [12], [51].
+ Tui thng pht hin bnh >30.
+ Khi pht chm, thng khng triu chng.
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43
+ Lm sng thng gp ngi bo ph, c tin s gia nh bnh
T tp 2.
+ Nhim toan ceton him gp.
+ Insulin mu: tng, bnh thng hoc gim nh.
Trong nghin cu ny chng ti chn bnh nhn i tho ng tp 2
c chn on trc ang iu tr bng thuc vin h ng huyt c
hoc khng c kt hp vi insulin.
2.1.1.3. Tiu chun loi tr
- Bnh nhn ang b cc bin chng nng ca T nh hn m tng
ng mu, iu tr cc bnh ni khoa nng c hn m, nhi mu c tim,
bnh phi mn tnh nng, vim khp dng thp, bnh nhn tn thng
thnkhng cho php thc hin cc k thut thm d.
- Khng ng tham gia nghin cu.
2.1.2. Nhm chng tham chiu
tham chiu gi tr trung bnh nng MPO i tng T tp 2
so vi khng T, i tng c tham chiu l nhng ngi n khm
sc khe ti khoa Khm Bnh, bnh vin a khoa Trung tm Tin Giang,
khng mc cc bnh l nh hng n tng nng MPO.
- Tnh nguyn tham gia nghin cu.
2.1.3. a im v thi gian nghin cu
Tt c cc i tng tham gia nghin cu c thm khm lm sng
v thc hin cn lm sng ti Bnh vin a khoa Trung tm Tin Giang.
Ring xt nghim nh lng nng MPO huyt tng c thc
hin ti Bnh vin Trung ng Hu.
Thi gian nghin cu t thng 01 nm 2011 n thng 12 nm 2013.
2.2. PHNG PHP NGHIN CU
2.2.1. Thit k nghin cu
Phng php nghin cu l m t, ct ngang c nhm chng tham
chiu nng MPO.
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44
2.2.2. Cch thc chn mu
C mu: theo cng thc tnh c mu tnh gi tr trung bnh nng
MPO gia 2 nhm:
1
21
22
ES
ES
CN
Trong
- 1: nng MPO trung bnh ca nhm tham chiu.
1= 130,9 pmol/l.
Kt qu gi tr trung bnh MPO nhm tham chiu ly t gi tr trung
bnh nhm chng ca nghin cu Shetty [151].
- 2: nng MPO trung bnh ca nhm bnh.
2=178,3pmol/l.
Kt qu gi tr trung bnh MPO ly t gi tr trung bnh MPO nhm
T tp 2 t nghin cu ca Shetty [151].
- 1: lch chun ca nhm tham chiu.
lch chun 1=61,7 ly t nghin cu ca Shetty [151].
- C:19,84 (ng vi =0,01; =0,05).
Kt qu tnh ton s n c mu cn thit cho mi nhm l 67.
Thc t mu nghin cu ca chng ti gm 2 nhm:
Nhm bnh T tp 2 gm 81 bnh nhn.
Nhm chng tham chiu gm 67 ngi.
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45
2.2.3. Cc bin s nghin cu
Tt c cc i tng T c nghin cu cc tham s bao gm:
2.2.3.1. Yu t nguy c truyn thng
- Tui: Tnh theo nm sinh dng lch ca bnh nhn.
Da vo cc khuyn co nguy c tim mch tui 55 t [85], [121].
Chng ti chia tui c chia thnh 3 nhm: nhm 1:
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46
mc tiu kim sot HA da vo ADA 2014, bnh nhn T mc tiu kim
sot l HA
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47
2.2.3.2. Yu t nguy c khng truyn thng
- Vng bng (VB)
+ Phng php tin hnh: Bnh nhn ng thng, 2 bn chn dng 10
cm, th u, dng thc dy (n v tnh l cm) o VB vo cui k th ra.
Vng bng o ngang qua trung im gia xng sn cui v mo chu (i
vi ngi qu bo ph). Sai s khng qu 0,5cm.
+ nh gi kt qu: Ch s VB c nh gi theo tiu chun ca Lin
on i tho ng Quc t nm 2005 dnh cho ngi Chu , VB c
xem l c nguy c khi nam 90cm v n 80cm [129].
- Ch s khi c th (BMI)
+ Phng php tin hnh: Cn t v tr cn bng. i tng trong t
th ng thng thoi mi, mt nhn v pha trc, 2 gt chn st mt sau ca
cn chm li thnh hnh ch V. i chn trn, khng i m, khng mang bt
c vt g, ch mc o qun mng. m bo 4 im trn c th chm vo thc
o l vng chm, xng b vai, mng v gt chn.
o cn nng c th. Kt qu tnh bng kg, sai s khng qu 100g.
o chiu cao c th bng thc o chiu cao gn lin vi cn. Bnh
nhn ng trong t th nh o cn nng. Ngi o ko ke gn sn trn thc
o ln cho qu u, h xung n chm nh u. Kt qu tnh bng n v m,
sai s khng qu 10mm [1].
+ n v dng: Cn nng (CN)= kg; Chiu cao (CC)= m.
+ Tnh ch s khi c th (BMI) theo cng thc: BMI= 2mCCkgCN
+ nh gi kt qu theo tiu chun phn bo ph ca WHO p dng
cho ngi Chu - Thi Bnh Dng [129].
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48
Bng 2.1. Phn bo ph p dng cho ngi Chu - Thi Bnh Dng
BMI (kg/m2) Phn
< 18,5
18,5-22,9
23,0-24,9
25,0-29,9
30,0
Gy
Bnh thng
Tha cn
Bo ph 1
Bo ph 2
- Glucose mu lc i: Cho bnh nhn nhn i qua m ti thiu 10
gi. Ly ng mu sng hm sau, trc n sng, lm xt nghim ti khoa
sinh ho Bnh vin a khoa Trung tm Tin Giang.
n v tnh l mmol/L.
nh gi iu tr: Theo ADA 2014, ng mu lc i t 3,9-7,2
mmol/L (70-130 mg/dL) gi l c kim sot tt [47].
- HbA1C: L loi huyt sc t c glycosyl ha, sn phm to
thnh glucose hoc dn xut phosphoryl ca glucose ln gc valin ca u
N tn ca chui ca huyt sc t A. Bnh nhn c ly mu vo bui
sng hm sau cng mu mu vi lm ng mu lc i. Lm xt nghim
ti khoa sinh ha bnh vin.
n v tnh l %. nh gi iu tr: Theo ADA 2014, HbA1C < 7% gi
l T kim sot tt [47].
- CRP: n v tnh l mg/L. loi nhng trng hp CRP tng do
bnh l vim cp, chng ti ch chn nhng trng hp c CRP20mg/L.
nh gi nguy c tim mch qua nng CRP huyt thanh theo
AHA/CDC 2003 [43], [138].
+ CRP < 1mg/L: nguy c tim mch thp.
+ CRP = 1-3mg/L: nguy c tim mch trung bnh.
+ CRP > 3mg/L: nguy c tim mch cao.
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49
- Fibrinogen huyt tng: Nng fibrinogen huyt tng (mg/l) c
o khoa xt nghim ti bnh vin ly mu nghin cu.
Ly mu tnh mch, thng l mt trong khy tay hay trn mt mu
bn tay.
Bnh thng theo chun my l: 200 - 400 mg/dl.
- Bch cu trung tnh: Bng my m ti khoa xt nghim ti bnh
vin ly mu nghin cu. Gi tr bnh thng ca bch cu chun theo my
l: 5.000-10.000 bch cu/ mm3 (5-10 G/L)
- o b dy lp trung ni mc ng mch cnh (IMT): My siu m
Mylab 50 Xvision ca hng Esaote, u d tn s 7,5 MHz c gn h thng
my vi tnh, tnh ton cc thng s t ng theo chng trnh. o IMT da
theo hng dn ca ASE 2008 [155].
+ T th bnh nhn: Nm nga, u quay 45 v pha i din
bn khm.
Hnh 2.1. V tr t u d o IMT ng mch cnh [155]
+ V tr o: Trc ch chia i ca ng mch cnh chung 10 mm.
+ Cch ly hnh nh b dy lp ni trung mc: Hnh nh cu trc thnh
ng mch qua siu m 2D, ct dc gm 3 lp. Lp ni mc (intima) v lp
ngoi (adventitia) to ra 2 ng hi m (echogenic) song song v chen gia
l lp gia (media) khng hi m.
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50
Trn siu m c th thy ng trong cng tng i r l lp ni mc,
ng en k tip l lp gia v ng trng ngoi cng l lp ngoi ca
ng mch.
B dy lp ni trung mc ng mch cnh chung trn siu m c tnh
t bt u ca lp ni mc pha trong lng mch, l lp hi m u tin,
ngang qua vng gim hi m n bt u ca lp ngoi mc (ranh gii ca
lp ngoi - trung mc), lp hi m th hai [178].
o khong cch t im trn b mt lp ni mc pha lng mch thng
gc tng xng n im nm trn ranh gii lp ngoi - trung mc.
o t nht 3 im khc nhau v tr kho st, b dy lp IMT c tnh
theo cng thc:
R = yin
i
n1
1
R: L b dy trung bnh cng lp IMT ti v tr kho st. n v biu th mm.
n: S im kho st.
yi: B dy lp ni trung mc ti im i.
n v biu th l mm.
+ nh gi IMT ng mch cnh chung theo hng dn ca Hi Tng
huyt p Chu u/ Hi Tim mch Chu u nm 2007 [121], [123], [143].
IMT 50% so vi b
dy ca on thnh mch k cn, khu tr, nh vo lng mch hoc khi
IMT 1,5mm.
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51
Hnh 2.2. Cch o b dy lp ni trung mc (IMT)
- in tim: Cho bnh nhn nm nga, bc l ngc, 2 tay xui dc
thn mnh, 2 chn dui thng, ci b cc trang sc c tnh dn in. Bi
kem dn in, mc cc in cc cc chi v trc tim theo quy nh ca Hi
Tim mch Hoa K. Tin hnh o 12 chuyn o thng dng.
Tc my o l 25mm/giy, bin l ng k ngang mi
1mV=1mm, thi gian l ng k dc mi 1mm=0,04 giy (my ci
chng trnh t ng ha).
Cch o QT v nh gi kt qu: Ly QT tiu biu V2 hay V4, nhng
nu kh khn (nh T dt, kh c) th ly D2. Trng hp c sng U qu
cao chng tip vo sn sng T lm d nhm vi vi phn ui ca sng T
nn lm khong QT di ra mt cch sai lm. Trng hp ny phi so snh
QT nhiu chuyn o. V QT ca mt nht bp ph thuc rt nhiu vo
tn s tim tc thi trc n nn khi o QT bao gi cng phi o khong
RR trc n. Khng nn o QT 3-4 phc b lin tip lin sau mt ngoi
tm thu v lc tnh dn truyn c bn ca c tim b ngoi tm thu tm
thi lm bin i, lm QT cng b bin i theo.
Phn tch on QT, tnh QTc theo cng thc Bazett: QTc = QT/ RR
(ms) [115]. Thi gian QTc l dng cng thc ton hc chuyn thi gian
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52
QT thc t thnh thi gian QT ca mt chu chuyn tim c tn s khong 60
ln/pht, xem n c nm trong gii hn bnh thng hay khng.
QTc 440 ms c xem l bnh l [115].
+ Ch s Sokolow-Lyon: nh gi dy tht tri, chng ti da vo
ch s Sokolow- Lyon c WHO cng nhn: SV1+RV5 hoc RV6 35
mm. Hoc RV5 hay RV6 >26 mm.
+ Thiu mu cc b c tim: Tiu chun chn on thiu mu c tim di
ni mc:
ST chnh xung1mm ti im J.
ST chnh xung dng, v sng T dng hay o ngc hng vi QRS.
ST chnh xung ti thi im J t 1-2mm, theo sau bi s chch ln ca
ST nhng vn di ng ng in 1mm v ko di 0,08 giy.
ST o ngc, su, i xng: Thiu mu di thng tm mc.
Tiu chun chn on nhi mu c tim mn: Q rng sng R cng
chuyn o.
- Siu m tim: Thc hin ti phng siu m tim ti bnh vin ly mu.
Sau khi gii thch r v cuc thm khm, cho bnh nhn nm ngh 5-10
pht, kim tra my, mc cc in cc o in tm cng lc.
Bnh nhn nm nghing tri mt gc khong 45o, ci b trang sc
c tnh dn in, bc l ngc, bi gel siu m, ngi khm ngi bn phi
bnh nhn.
Dng u d sector in t 3,5 MHz. Tin hnh siu m tun t bng siu
m 2 bnh din, siu m 1 bnh din, siu m Doppler xung v lin tc. hn
ch nh hng ca h hp ln ph Doppler nn o cui k th ra, tt c cc
thng s siu m tim c o trn 3 chu chuyn tim lin tip c mc in tm
ng thi. Kt qu cui cng l trung bnh cng ca cc gi tr ny.
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53
Cc php o trn siu m TM v 2D: t u d lin sn 2-3 cnh c
tri, kho st ton b tim qua siu m 2D mt ct cnh c trc dc, sau cc
thng s trn siu m TM. Chng ti s dng 2 nht ct: nht ct qua tht ghi
di b t do ca van 2 l v nht ct qua ng mch ch o theo khuyn co
ca Hi siu m tim Hoa K (2005).
+ ng knh tht tri cui tm trng (LVDd): o khi u ca phc
b QRS, t b di vch lin tht ti b trn ca thnh sau tht tri. Bnh
thng LVDd: 39-56 mm.
+ ng knh tht tri cui tm thu (LVDs): o t nh vn ng ra sau
ca vch lin tht ti b trn ca thnh sau tht tri. Bnh thng 22-43 mm.
+ Chiu dy vch lin tht cui tm trng (IVSd): o khi u ca
phc b QRS, t b trn ti b di ca vch lin tht. Bnh thng 6-11mm.
+ Chiu dy vch lin tht cui tm thu (IVSs), bnh thng 9-15 mm.
Chiu dy thnh sau tht tri cui tm thu (LVPWs), bnh thng 13-20mm.
+ Chiu dy thnh sau tht tri cui tm trng (LVPWd): o khi u
ca phc b QRS, t b trn thnh sau ti lp thng tm mc thnh sau.
Bnh thng 8-12 mm.
T cc ch s o c trn tnh c ch s khi c tht tri, chc nng
tm thu tht tri.
(1) Ch s khi c tht tri (LVMI)
Ch s khi c tht tri tnh theo cng thc c lp sn trn my t cc
ch s o c trn [147], [175].
LVMI(g/m2 ) = LVM (g)/BSA(m2)
Trong : LVM: khi c tht tri v BSA: din tch da c th
BSA = cn nng0,425(kg) x chiu cao 0,725(cm) x 71,84 x 10-10
LVM(g)= 0,8[1,04(LVDd+IVSd+ PWd)3 LVDd3] + 0,6
-
54
Theo tiu chun ca Hi siu m Hoa K (ASE- American Society of
Echocardiography) 2005, chn on ph i tht tri khi: LVMI >115 (g/m2)
i vi nam, LVMI > 95(g/m2) i vi n [147].
(2) Phn sut tng mu (EF):
c tnh theo cng thc sau: EF=(Vd Vs)/Vd
Trong : Vd v Dd l th tch v ng knh tht tri tm trng.Vs v
Ds l th tch v ng knh tht tri tm thu.
Vd = 7x LVDd3/2,4 x LVDd
Vs = 7x LVDs3/ 2,4 x LVDs
+ nh gi ri lon chc nng tm thu tht tri theo ASE (2005) [116]
Chc nng tm thu gim nng: EF < 30%
Chc nng tm thu gim va: 30% EF 44%
Chc nng tm thu gim nh: 45% EF 54%
Chc nng tm thu bnh thng: 55% EF < 80%
- nh lng nng enzyme myeloperoxidase huyt tng
ARCHITECT MPO l mt xt nghim theo k thut in ha pht quang
vi ht, nh lng nng MPO huyt tng trn h thng my xt nghim
min dch t ng ARCHITECT ca hng Abbott [44], c ch chy cp
cu, c thc hin ti khoa sinh ha BV TW Hu.
n v biu th: pmol/l
Phng php: CMIA, Sandwich.
La chn khng th: khng th gn v khng th pht tn hiu ngun gc
chut n dng.
Loi mu bnh phm: Huyt tng vi cht chng ng EDTA.
Xt nghim ARCHITECT MPO ang pht trin l xt nghim min dch
gm 2 bc xc nh s hin din MPO ca ngi trong huyt tng bng
cch s dng k thut ha pht quang min dch t ng (chemiluminescent
-
55
automated immunoassay CMIA) xt nghim vi cc giao thc linh hot, c
gi l CHEMIFLEX. C th c thc hin ch thng xuyn hoc STAT.
Trong bc u tin, mu cha MPO v khng MPO mng thun t
phn vi th c kt hp. MPO hin din trong mu th lin kt vi cc
khng MPO mng phn vi th.
Bc th hai sau khi ra, khng MPO acridinium lin hp c dn
nhn v chuyn sang bc tip theo.
Tip theo mt bc v ra khc, pre - trigger v dung dch trigger
c thm vo hn hp phn ng.
Kt qu phn ng pht quang ha hc c o l n v nh sng tng
i (relative light units - RLUs). Mt mi lin quan trc tip tn ti gia s
lng ca MPO trong mu th v cc RLUs pht hin bi cc h thng quang
hc ARCHITECT. Nng ca MPO c c lin quan n mt ng
cong tiu chun thnh lp vi nng MPO chun c bit trc.
Khong o: 0-10000 pmol/l
Thi gian ra kt qu u tin: 18 pht
Nng MPO thc hin trong 149 mu khe mnh, nng trung bnh
l 190 pmol/l. Mt nghin cu khc thc hin 400 mu. Nng trung bnh l
285,5 pmol/l (95%) [44].
Cch thu thp, bo qun v vn chuyn mu: Mu sau khi c ly t
bnh nhn c b vo tup c cha cht chng ng EDTA, y np, dn
nhn, ghi y thng tin bnh nhn, chuyn n phng xt nghim t th
ng thng. Ti phng xt nghim sau khi mu c tip nhn s c quay
ly tm tch huyt tng sau c bo qun trong nhit thch hp
(khong -180C) v m bo mu c duy tr nhit thch hp trong sut
thi gian vn chuyn n ni xt nghim.
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56
2.2.4. Phng php thu thp v x l s liu
2.2.4.1. Phng php thu thp s liu
Cc s liu lm sng, cn lm sng v nhng thng tin khc c ghi
nhn vo phiu nghin cu chung.
2.2.4.2. Phng php x l s liu
- X l s liu trn my vi tnh bng phn mm thng k SPSS 16.0.
- Gi tr cc ch s nh lng c trnh by di dng trung bnh
lch chun (SD).
Cch tnh tr s trung bnh:
n
n
ixn
X1
1
Trong x l tr s ca c th, n l tng s cc trng hp.
lch chun (SD): 1
)(1
2
n
xx
SD
n
i
i
- nh gi s khc bit gia 2 gi tr trung bnh bng kim nh t-test.
t =
ba
p
ba
nnS
XX
11
)(
X : Trung bnh mu. S: phng sai
- Cc ch s nh tnh c trnh by di dng t l phn trm (%).
Dng cng thc kim nh Z so snh hai t l ca hai tng th.
Z =
)11
)(1( 00BA
BA
nnPP
PP
P A = A
A
n
X; P B =
B
B
n
X ; P 0 =
BA
BA
nn
XX
- nh gi s khc bit c ngha thng k khi p < 0,05 [135].
- nh gi s tng quan theo h s tng quan Pearson (r) [112].
-
57
r =
n
i
n
i
ii
n
i
ii
yyxx
yyxx
1 1
22
1
)()(
))((
+ r > 0: tng quan thun.
+ r < 0: tng quan nghch.
- Thit lp ng cong ROC bng phn mm SPSS 16.0.
Din tch di ng cong ROC c nh gi nh sau:
+ Din tch di ng cong < 0,6: Khng c gi tr d bo.
+ Din tch di ng cong t 0,6-0,7: C gi tr d bo trung bnh.
+ Din tch di ng cong t