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PENGARUH PEMBERIAN EKSTRAK KULIT MANGGIS
(Garcinia mangostana) DAN SIMVASTATIN TERHADAP
KADAR KOLESTEROL HDL TIKUS Sprague dawley
DENGAN PAKAN TINGGI LEMAK
LAPORAN HASIL
KARYA TULIS ILMIAH
Disusun untuk memenuhi sebagian persyaratan
guna mencapai gelar sarjana strata -1 kedokteran umum
INGE KURNIAWATI ADIPRATAMA
22010110120140
PROGRAM PENDIDIKAN SARJANA KEDOKTERAN
FAKULTAS KEDOKTERAN
UNIVERSITAS DIPONEGORO
2014
iv
KATA PENGANTAR
Puji syukur penulis panjatkan ke hadirat Tuhan Yang Maha Esa, karena
atas rahmat dan karunia- Nya penulis dapat menyelesaikan Karya Tulis Ilmiah ini.
Penulisan Karya Tulis Ilmiah bertujuan untuk memenuhi sebagian persyaratan
guna mencapai derajat Sarjana Strata – 1 Kedokteran Umum di Fakultas
Kedokteran Universitas Diponegoro Semarang. Kami menyadari sangatlah sulit
bagi kami untuk menyelesaikan Karya Tulis Ilmiah ini tanpa bantuan dan
bimbingan dari berbagai pihak sejak penyusunan proposal sampai dengan
terselesaikannya laporan hasil Karya Tulis Ilmiah ini. Bersama ini, penulis
mengucapkan terima kasih dan penghargaan setinggi-tingginya kepada:
1. Prof. Sudharto P Hadi, MES, PhD selaku Rektor Universitas Diponegoro
Semarang yang telah memberikan kesempatan kepada penulis untuk belajar
dan meningkatkan ilmu pengetahuan.
2. dr. Endang Ambarwati, Sp.RM selaku Dekan Fakultas Kedokteran Universitas
Diponegoro Semarang yang telah memberikan sarana dan prasarana sehingga
penulis dapat menyelesaikan Karya Tulis Ilmiah ini dengan baik.
3. dr. Kusmiyati Tjahjono DK, M.Kes selaku dosen pembimbing I dan dr.
Amallia N. Setyawati, M.Si. Med, selaku dosen pembimbing II, yang telah
meluangkan waktu, tenaga dan pikiran untuk memberikan bimbingan kepada
penulis selama penyusunan Karya Tulis Ilmiah ini.
4. dr. Budhi Surastri Soejoto, M.Si. Med selaku ketua penguji dan dr. Dwi
Ngestiningsih, M.Kes.,Sp.PD selaku penguji Karya Tulis ilmiah ini.
5. Segenap staf LPPT-LP3HP Universitas Gadjah Mada Yogyakarta yang telah
membantu dalam proses penelitian.
6. Orang tua dan keluarga yang senantiasa memberi dukungan moral maupun
material.
7. Para sahabat yang senantiasa memberi dukungan dalam penyelesaian Karya
Tulis Ilmiah.
v
8. Semua pihak yang tidak dapat penulis sebutkan satu-persatu atas bantuan secara
langsung maupun tidak langsung sehingga Karya Tulis Ilmiah ini dapat
diselesaikan.
Akhir kata, saya berharap Tuhan Yang Maha Esa membalas kebaikan
semua pihak yang telah bersedia membantu. Semoga Karya Tulis Ilmiah ini dapat
bermanfaat bagi kita semua.
Semarang, 18 Juli 2014
Penulis
vi
DAFTAR ISI
HALAMAN JUDUL ............................................................................................ i
LEMBAR PENGESAHAN .................................................................................. ii
PERNYATAAN KEASLIAN .............................................................................. iii
KATA PENGANTAR ......................................................................................... iv
DAFTAR ISI ........................................................................................................ vi
DAFTAR TABEL ................................................................................................ ix
DAFTAR GAMBAR ... ....................................................................................... x
DAFTAR LAMPIRAN ....................................................................................... xi
DAFTAR SINGKATAN ..................................................................................... xii
ABSTRAK ........................................................................................................... xiii
ABSTRACT .......................................................................................................... xiv
1.1 Latar belakang ................................................................................................ 1
1.2 Permasalahan penelitian ................................................................................. 4
1.3 Tujuan penelitian ............................................................................................ 4
1.3.1 Tujuan umum ............................................................................................... 4
1.3.2 Tujuan khusus .............................................................................................. 4
1.4 Manfaat penelitian ......................................................................................... 5
1.5 Keaslian penelitian ......................................................................................... 6
BAB 2 TINJAUAN PUSTAKA
2.1 Lipid ............................................................................................................... 8
2.1.1 Definisi dan Fungsi Lipid ........................................................................... 8
2.1.2 Lipid plasma dan lipoprotein ....................................................................... 8
2.1.2.1 Kilomikron ................................................................................................ 9
2.1.2.2 Very Low Density Lipoprotein (VLDL) ................................................... 9
2.1.2.3. Low Density Lipoprotein (LDL) ............................................................. 10
2.1.2.4 High Density Lipoprotein (HDL) ............................................................. 10
2.1.3 Apolipoprotein ............................................................................................ 13
vii
2.3 Absorbsi dan transport lipid ........................................................................... 15
2.4 Dislipidemia ................................................................................................... 15
2.5 Profil lipid serum ........................................................................................... 16
2.6 Faktor risiko perubahan kadar kolesterol HDL .............................................. 17
2.6 Ekstrak kulit manggis ...................................................................................... 19
2.6.1 Tanaman manggis ........................................................................................ 19
2.6.2 Manfaat ekstrak kulit manggis .................................................................... 19
2.6.3 Ekstrak kulit manggis sebagai antilipemik ................................................. 20
2.7 Simvastatin ..................................................................................................... 21
2.7.1. Efek samping .............................................................................................. 21
2.7.2 Penggunaan ................................................................................................. 22
BAB 3 KERANGKA TEORI, KERANGKA KONSEP, DAN HIPOTESIS
3.1 Kerangka teori ................................................................................................ 23
3.2 Kerangka konsep ............................................................................................ 23
3.3 Hipotesis ......................................................................................................... 24
3.3 1 Hipotesis mayor ......................................................................................... 24
3.3.2 Hipotesis minor ........................................................................................... 24
BAB 4 METODE PENELITIAN
4.1 Ruang lingkup penelitian ............................................................................... 25
4.2 Tempat dan waktu penelitian ........................................................................ 25
4.3 Jenis dan rancangan penelitian ....................................................................... 25
4.4 Populasi dan sampel ....................................................................................... 27
4.4.1 Sampel ......................................................................................................... 27
4.4.1.1 Kriteria inklusi ......................................................................................... 27
4.4.1.2 Kriteria eksklusi ...................................................................................... 27
4.4.2 Cara sampling .............................................................................................. 27
4.4.3 Besar sampel ............................................................................................... 28
4.5 Variabel penelitian ........................................................................................ 28
4.5.1 Variabel bebas ............................................................................................. 28
4.5.2 Variabel terikat ............................................................................................ 28
viii
4.6 Definisi operasional ....................................................................................... 29
4.7 Cara pengumpulan data ................................................................................... 30
4.7.1 Bahan ........................................................................................................... 30
4.7.2 Alat .............................................................................................................. 30
4.7.3 Jenis data .................................................................................................... 31
4.7.4 Cara kerja .................................................................................................... 31
4.7.4.1 Aklimatisasi ............................................................................................. 31
4.7.4.2 Pengelompokan ......................................................................................... 31
4.7.4.3 Pemberian perlakuan ................................................................................ 32
4.7.4.4 Pengambilan data ..................................................................................... 33
4.8 Alur Penelitian ............................................................................................... 34
4.9 Analisis data ................................................................................................... 35
4.10 Etika penelitian ............................................................................................. 36
4.11 Konflik kepentingan ..................................................................................... 36
4.2 Jadwal penelitian ........................................................................................... 36
HASIL PENELITIAN .......................................................................................... 37
PEMBAHASAN .................................................................................................. 43
SIMPULAN DAN SARAN ................................................................................. 51
DAFTAR PUSTAKA .......................................................................................... 52
ix
DAFTAR TABEL
Tabel 1. Keaslian penelitian ................................................................................. 6
Tabel 2. Karakteristik dan komposisi lipoprotein ................................................ 14
Tabel 3. Kadar lipid serum normal ...................................................................... 17
Tebel 4. Definisi operasional ............................................................................... 29
Tabel 5. Jadwal penelitian .................................................................................... 36
Tabel 6. Berat badan rata – rata tikus ................................................................... 38
Tabel 7. Analisis kadar kolesterol HDL ................................................................ 40
Tabel 8. Uji Normalitas ........................................................................................ 41
Tabel 9. Komposisi pakan standar ....................................................................... 58
Tabel 10. Komposisi pakan tinggi lemak ............................................................. 58
x
DAFTAR GAMBAR
Gambar 1. Rancangan penelitian ....................................................................... 26
Gambar 2. Diagram alur penelitian .................................................................... 34
Gambar 3. Grafik rata- rata kadar kolesterol HDL ............................................ 40
xi
DAFTAR LAMPIRAN
Lampiran 1. Komposisi pakan ............................................................................. 41
Lampiran 1.1 Komposisi pakan standar ............................................................... 41
Lampiran 1.2 Komposisi pakan tinggi lemak ...................................................... 41
Lampiran 2. Prosedur Sampling Retroorbital ....................................................... 42
Lampiran 3. Lembar kerja Uji Kimia ................................................................... 60
Lampiran 4. Ethical clearance .............................................................................. 61
Lampiran 5. Permohonan Ethical clearance ......................................................... 62
Lampiran 6. Permohonan ijin penelitian .............................................................. 63
Lampiran 7. Ijin penelitian ................................................................................... 64
Lampiran 8. Hasil laboratorium kelompok kontrol ............................................. 65
Lampiran 9. Hasil laboratorium kelompok perlakuan ......................................... 66
Lampiran 10. Surat keterangan ............................................................................ 67
Lampiran 11. Dokumentasi penelitian ................................................................. 68
Lampiran 12. Analisis statistik ............................................................................. 69
Lampiran 13. Biodata Mahasiswa ......................................................................... 78
xii
DAFTAR SINGKATAN
ABCA 1 : Hepatic ATP-Binding Cassette Transporter A1
CETP : Cholesterol Ester Transfer Protein
CHOD-PAP : Cholesterol Oxydase - Phenyl Aminopyrazolon
CK : Creatin Kinase
FDA : Food and Drug Administration
FFA : Free Fatty Acid
HDL : High Density Lipoprotein
HMG-KoA : 3-hidroksi-3-metilglutaril koenzim A
HTGL : Hepatic Triglyceride Lipase
IDL : Intermediate Density Lipoprotein
KEPK : Komisi Etik Penelitian Kesehatan
LCAT : Cholesterol Acyl Transferase
LDL : Low Density Lipoprotein
LP : lipoprotein
LPL : Lipoprotein Lipase Lechitin
MONICA : Monitoring Trends and Determinants of Cardiovascular Disease
OH : hidroksida
ORAC : Oxygen Radical Absorbance Capacity
PPAR : Peroxisome Proliferators-Activated Receptors
RCT : Reverse Cholesterol Transport
rLDL : reseptor kolesterol LDL
SR-B1 : reseptor scavenger kelas B tipe 1
TG : trigliserida
VLDL : Very Low Density Lipoprotein
xiii
ABSTRAK
Latar Belakang Dislipidemia merupakan kelainan metabolisme lipid yang
ditandai oleh peningkatan atau penurunan fraksi lipid plasma, salah satu kelainan
adalah penurunan kadar HDL. Ekstrak kulit manggis (Garcinia mangostana)
menurut penelitian terdahulu mengandungan xanthone diperkirakan dapat
meningkatkan kadar kolesterol HDL. Terapi farmakologis yang digunakan untuk
dislipidemia adalah Simvastatin. Penelitian mengenai gabungan keduanya
terhadap kadar kolesterol HDL belum pernah dilakukan.
Tujuan Melihat perbedaan efektivitas ekstrak kulit manggis (Garcinia
mangostana) dengan simvastatin terhadap peningkatan kadar kolesterol HDL.
Metode Penelitian Eksperimental Post Test Only Control Group Design.
Sampel 35 tikus Sprague dawley jantan dibagi menjadi 5 kelompok. Kontrol
negatif (K1), kontrol positif (K2), dan kelompok tikus yang mendapat terapi
ekstrak kulit manggis dosis 400 mg/kgBB/hari (P1), simvastatin dosis 0,18
mg/200 gBB/hari (P2), ekstrak kulit manggis dosis 400 mg/kgBB/hari ditambah
simvastatin dosis 0,18 mg/200 gBB/hari (P3). Tikus diinduksi dengan pakan tinggi
lemak (kecuali K1) dalam 4 minggu, kemudian kolesterol HDL untuk kelompok
kontrol diukur. Setelah 4 minggu, tikus dalam kelompok P1, P2, P3 diberikan
pakan standar dan terapi selama 4 minggu kemudian, setelah itu dilakukan
pengukuran kadar kolesterol HDL.
Hasil Rata rata kadar kolesterol HDL Kelompok K1 28,19, kelompok K2 29,36,
Kelompok P1 24,33, Kelompok P2 30,51, Kelompok P3 24,09. Pada Uji Anova
diperoleh tidak ada perbedaan yang signifikan (p=0,310)
Kesimpulan Ekstrak kulit manggis dan kombinasi ekstrak kulit manggis dan
simvastatin menurunkan kadar kolesterol HDL dan simvastatin meningkatkan
kadar kolesterol HDL tikus Sprague dawley setelah induksi pakan tinggi lemak.
Kata kunci: Garcinia mangostana, simvastatin, kolesterol HDL
xiv
ABSTRACT
Background Dyslipidemia is a disorder of lipid metabolism characterized by
increase or decrease in plasma lipid fractions, one of the abnormalities is
reduction of HDL cholesterol level. Extract of Mangosteen pericarp (Garcinia
mangostana) suspected in the researches before contains xanthone that may
increase the HDL cholesterol. Pharmacologically management for dyslipidemia
are simvastatin. There was not conducted research about the effect of
combination both in HDL cholesterol level.
Aim To determine the effect of extract of mangosteen pericarp and simvastatin
to the HDL cholesterol level in Sprague dawley mice.
Methods Experimental study Post Test Only Control Group Design. Thirty five
male Sprague dawley rats were divided randomly into five groups, comprised of
groups that were negative control (K1), positive control (K2) and treatments
groups receiving therapy mangosteen pericarp extract dose 400mg/kgBW/day for
P1, simvastatin dose 0,18 mg/200 gBW/day for P2, and mangosteen pericarp
extract dose 400mg/kgBW/day plus simvastatin dose 0,18 mg/200 gBW/day for
P3. The model groups are induced high content of lipids diet (except K1) for 4
weeks then cholesterol HDL level were measured for control groups. After 4
weeks, experimental animals (P1, P2, P3) given normal diet and therapys for 4
weeks later then cholesterol HDL level were measured.
Results HDL cholesterol level mean were 28,19 for K1, 29,36 for K2, 24,33 for
P1, 30,51 for P2, 24,09 for P3. One way Anova analysis showed non significant
differences (p=0,310)
Conclusions Extract of mangosteen (Garcinia mangostana) pericarp and
combination of extract of mangosteen pericarp plus simvastatin decrease HDL
level and simvastatin increase HDL cholesterol level in high content of lipids diet
in rats serum.
Key Words: Garcinia mangostana, simvastatin, HDL cholesterol
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