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

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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.

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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

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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

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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

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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

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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

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DAFTAR GAMBAR

Gambar 1. Rancangan penelitian ....................................................................... 26

Gambar 2. Diagram alur penelitian .................................................................... 34

Gambar 3. Grafik rata- rata kadar kolesterol HDL ............................................ 40

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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

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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

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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

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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