KARYA TULIS AKHIR

Pengaruh Pemberian Minyak Zaitun Ekstra Virgin Terhadap Penurunan Kadar LDL Tikus Putih Model Diabetes Mellitus

Oleh :

SANDY PRANADA

NIM 201310330311139

FAKULTAS KEDOKTERAN

UNIVERSITAS MUHAMMADIYAH MALANG

2017

i

KARYA TULIS AKHIR

Pengaruh Pemberian Minyak Zaitun Ekstra Virgin Terhadap Penurunan

Kadar LDL Tikus Putih Model Diabetes Mellitus

Diajukan kepada

Universitas Muhammadiyah Malang untuk memenuhi

salah satu persyaratan dalam menyelesaikan

Program Sarjana Fakultas Kedokteran

Oleh:

Sandy Pranada

201310330311139

FAKULTAS KEDOKTERAN

UNIVERSITAS MUHAMMADIYAH MALANG

2017

ii

LEMBAR PENGESAHAN

LAPORAN HASIL PENELITIAN

Telah disetujui sebagai hasil penelitian untuk memenuhi persyaratan

Pendidikan Sarjana Fakultas Kedokteran Universitas Muhammadiyah Malang

Tanggal : 19 Juli 2017

Pembimbing I

dr. Moch. Bahrudin, Sp.S

Pembimbing II

dr. Bambang Widiwanto, Sp.OT

Mengetahui, Fakultas Kedokteran Universitas Muhammadiyah Malang

Dekan,

dr. Irma Suswati, M.Kes

iii

PERNYATAAN ORISINALITAS

Karya tulis akhir ini adalah karya saya sendiri, dan semua sumber baik yang dikutip

maupun dirujuk telah saya nyatakan dengan benar.

Nama : Sandy Pranada

NIM : 201310330311139

Malang, 19 Juli 2017

Penulis

iv

LEMBAR PENGUJIAN

Karya Tulis Akhir oleh Sandy Pranada ini telah diuji dan dipertahankan didepan tim penguji

pada tanggal 19 Juli 2017

Tim Penguji

dr. Moch. Bahrudin, Sp.S , Ketua

dr. Bambang Widiwanto, Sp.OT , Anggota

dr. Febri Endra Budi Setyawan, M.Kes , Anggota

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KATA PENGANTAR

Assalamu’alaikum Warahmatullah Wabarakatuh

Puji syukur kehadirat Allah SWT yang Maha Pengasih lagi Maha Penyayang

atas nikmat Iman dan Islam serta nikmat kesehatan dan kesempatan, atas izin Allah

SWT penulisan tugas akhir ini dapat selesai dengan baik. Shalawat serta salam

semoga senantiasa tercurahkan kepada Rasulullah Muhammad SAW, keluarganya

para sahabat dan para pengikutnya yang telah berjuang dalam dakwah dan syiar

Islam.

Penelitian tugas akhir ini berjudul “Pengaruh Pemberian Minyak Zaitun

Ekstra Virgin Terhadap Penurunan Kadar LDL Tikus Putih Model Diabetes

Mellitus”. Tugas akhir ini diajukan untuk memenuhi persyaratan Pendidikan Sarjana

Fakultas Kedokteran Universitas Muhammadiyah Malang.

Penulis menyadari tugas akhir ini masih jauh dari kata sempurna, oleh karena

itu, penulis sangat mengharapkan saran dan masukan yang membangun. Semoga

karya tulis ini dapat menambah wawasan keilmuan dan bermanfaat bagi para pencari

ilmu.

Wassalamu’alaikum Warahmatullah Wabarakatuh

Malang, 19 Juli 2017

Penulis

vi

UCAPAN TERIMAKASIH

1. dr. Irma Suswati, M.Kes, selaku Dekan Fakultas Kedokteran Universitas

Muhammadiyah Malang atas ilmu dan bimbingannya selama menempuh studi

di Fakultas Kedokteran UMM.

2. dr. Moch. Ma’roef, Sp.OG, selaku Pembantu Dekan I Fakultas Kedokteran

UMM atas motivasi dan semangat mendidik dengan karakter.

3. dr. Rahayu, Sp.S, selaku Pembantu dekan II Fakultas Kedokteran UMM yang

senantiasa memberikan ilmu dan kebijaksanaan dalam profesi kedokteran.

4. dr. Iwan Sys Indrawanto, Sp.KJ, selaku Pembantu Dekan III, yang semangat

menyampaikan ilmu dan motivasi dalam menjalani pendidikan di FKUMM.

5. dr. Moch. Bahrudin, Sp.S, selaku pembimbing 1,atas kesabaran, kebaikan hati,

serta kesediaan dalam meluangkan waktu dalam membimbing hingga dapat

menyelesaikan penelitian ini dengan baik.

6. dr. Bambang Widiwanto, Sp.OT, selaku pembimbing 2, atas kesabaran,

kebaikan hati, serta kesediaan dalam meluangkan waktu dalam membimbing

penulis hingga dapat menyelesaikan penelitian ini dengan baik.

7. dr. Febri Endra Budi Setyawan, M.Kes, atas segala masukan dan arahan yang

sangat bermanfaat dalam pengerjaan tugas akhir ini dan atas kesediaan waktu,

sehingga tugas ini dapat diselesaikan dengan baik.

8. Kedua orang tua tercinta, Bapak Mundi Agung Budi Iswara dan Ibunda Arijani

Dian Puspa Dewi, serta kakak laki-laki saya Aldo Aditya dan kakak perempuan

vii

saya Saskia Rachmawati, terima kasih atas doa, dukungan, dan semangat yang

tidak henti-hentinya kepada penulis.

9. Seluruh staf tata usaha dan laboratorium, Mbak Dila, Mbak Lia, Mas Miftah,

Pak Joko, Mbak Patma, Mas Nyono, Pak Yono, Bu Endah, Mbak Citra dan

Mbak Nuke yang membantu proses penelitian hingga penyelesaian tugas akhir

ini.

10. Sejawat FK UMM angkatan 2013, Gluteus Maximus, atas dukungan dan

bantuan, semoga Allah senantiasa meridhoi setiap langkah kita, menjadi insan

dokter yang amanah dan sukses di dunia hingga akhirat

11. Keluarga besar TBMM Nurul Qolbi, terimakasih atas motivasi dan, dukungan

yang telah diberikan.

12. Semua pihak yang terlibat secara langsung maupun tidak langsung, penulis

menyampaikan terimakasih atas bantuan dan dukungannya. Semoga Allah

SWT senantiasa membalas dengan kebaikan yang berlimpah.

x

DAFTAR ISI

HALAMAN JUDUL DEPAN ................................................................................... i

LEMBAR PENGESAHAN ....................................................................................... ii

PERNYATAAN ORISINALITAS ............................................................................ iii

LEMBAR PENGUJIAN ............................................................................................ iv

KATA PENGANTAR ............................................................................................... v

UCAPAN TERIMAKASIH ....................................................................................... vi

ABSTRAK ................................................................................................................. viii

ABSTRACT ................................................................................................................. ix

DAFTAR ISI .............................................................................................................. x

DAFTAR TABEL ...................................................................................................... xiv

DAFTAR GAMBAR ................................................................................................. xv

DAFTAR LAMPIRAN .............................................................................................. xvi

DAFTAR SINGKATAN ........................................................................................ xvii

BAB 1 PENDAHULUAN

1.1 Latar Belakang ......................................................................................... 1

1.2 Rumusan Masalah .................................................................................... 2

1.3 Tujuan Penelitian ..................................................................................... 2

1.3.1 Tujuan Umum ........................................................................ 2

1.3.2 Tujuan Khusus ....................................................................... 3

1.4 Manfaat Penelitian ................................................................................... 3

1.4.1 Manfaat Akademik ................................................................. 3

1.4.2 Manfaat Klinis ........................................................................ 3

xi

1.4.3 Manfaat Masyarakat ............................................................... 3

BAB 2 TINAJAUAN PUSTAKA

2.1 Minyak Zaitun ......................................................................................... 4

2.1.1 Definisi ................................................................................... 4

2.1.2 Taksonomi Tanaman Zaitun .................................................. 5

2.1.3 Kandungan ............................................................................. 5

2.2 Diabetes Mellitus ..................................................................................... 6

2.2.1 Etiologi Diabetes Mellitus...................................................... 6

2.2.2 Patogenesis Diabetes Mellitus.…………..…………………..8

2.2.2.1 Patogenesis Diabetes Mellitus Tipe 1 ........................ 8

2.2.2.2 Patogenesis Diabetes Mellitus Tipe 2 ........................ 9

2.2.3 Diabetes Akibat Aloksan........................................................ 9

2.3 Profil Lipid ............................................................................................... 11

2.3.1 Klasifikasi Lipid ..................................................................... 11

2.3.1.1 Lipid Sederhana ......................................................... 11

2.3.1.2 Lipid Kompleks .......................................................... 11

2.3.1.3 Prekursor dan Lipid Turunan ..................................... 12

2.3.2 Lipoprotein ............................................................................. 12

2.3.2.1 Kilomikron ................................................................. 12

2.3.2.2 Very Low Density Lipoprotein (VLDL) ..................... 13

2.3.2.3 Low Density Lipoprotein (LDL) ................................ 13

2.3.2.4 High Density Lipoprotein (HDL) ............................... 13

2.3.3 Metabolisme Lipoprotein ....................................................... 14

2.3.3.1 Jalur Metabolisme Eksogen ....................................... 14

2.3.3.2 Jalur Metabolisme Endogen ...................................... 14

2.3.3.3 Jalur Reverse Cholesterol Transport .......................... 15

2.4 Dislipidemia ............................................................................................. 15

2.4.1 Mekanisme Dislipidemia ....................................................... 15

2.5 Peran Minyak Zaitun Terhadap Penurunan kadar LDL ........................... 16

xii

BAB 3 KERANGKA KONSEP DAN HIPOTESIS PENELITIAN

3.1 Kerangka Konsep Penelitian .................................................................... 18

3.2 Hipotesis Penelitian .................................................................................. 20

BAB 4 METODE PENELITIAN

4.1 Jenis Penelitian ......................................................................................... 21

4.2 Lokasi dan Waktu Penelitian .................................................................... 21

4.3 Populasi dan Sampel ................................................................................ 21

4.3.1 Populasi ..................................................................................... 21

4.3.2 Sampel ....................................................................................... 21

4.3.3 Besar Sampel ............................................................................. 21

4.3.4 Teknik Pengambilan Sampel ..................................................... 23

4.3.5 Karakteristik Sampel Penelitian ................................................ 23

4.3.5.1 Kriteria Inklusi ............................................................ 23

4.3.5.2 Kriteria Eksklusi ......................................................... 24

4.3.5.3 Kriteria Drop Out ........................................................ 24

4.3.6 Variabel Penelitian .................................................................... 24

4.3.6.1 Variabel Bebas ............................................................ 24

4.3.6.2 Variabel Tergantung ................................................... 24

4.3.7 Definisi Operasional .................................................................. 24

4.4 Alat dan Bahan Penelitian ........................................................................ 25

4.4.1 Alat ............................................................................................ 25

4.4.2 Bahan ......................................................................................... 26

4.5 Prosedur Penelitian ................................................................................... 26

4.5.1 Pembagian Kelompok Tikus ..................................................... 26

4.5.2 Adaptasi ..................................................................................... 27

4.5.3 Pemberian Aloksan .................................................................... 27

4.5.4 Dasar Penentuan Dosis Minyak Zaitun ..................................... 27

4.5.5 Perolehan Minyak Zaitun .......................................................... 28

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4.5.6 Pemberian Minyak Zaitun ......................................................... 28

4.5.7 Proses Anastesi dan Pembedahan Hewan Coba ........................ 29

4.5.8 Perlakuan Terhadap Hewan Coba Setelah Dibedah .................. 29

4.5.9 Pengukuran Kadar LDL ............................................................ 30

4.6 Alur Penelitian .......................................................................................... 31

4.7 Analisis Data ............................................................................................ 32

4.8 Jadwal Penelitian ...................................................................................... 33

BAB 5 HASIL PENELITIAN DAN ANALISIS DATA

5.1 Hasil Penelitian ........................................................................................ 34

5.2 Analisis Data ............................................................................................ 36

5.2.1 Uji Normalitas ........................................................................... 36

5.2.2 Uji Homogenitas ........................................................................ 36

5.2.3 Uji Anova .................................................................................. 37

5.2.4 Uji Post Hoc Bonferoni ............................................................. 37

5.2.5 Uji Regresi Linier ...................................................................... 38

BAB 6 PEMBAHASAN

6.1 Pembahasan .............................................................................................. 40

BAB 7 KESIMPULAN DAN SARAN

7.1 Kesimpulan ............................................................................................... 44

7.2 Saran ....................................................................................................... 44

DAFTAR PUSTAKA ................................................................................................ 45

LAMPIRAN ............................................................................................................... 49

xiv

DAFTAR TABEL

Tabel Halaman

4.1 Definisi Operasional............................................................................................. 24

4.2 Jadwal penelitian .................................................................................................. 33

5.1 Hasil Penelitian Kadar LDL Tikus ....................................................................... 34

5.2 Uji Normalitas ...................................................................................................... 36

5.3 Uji Kesamaan Ragam dengan Uji Levene ........................................................... 36

5.4 Hasil Uji Anova.................................................................................................... 37

5.5 Hasil Uji Post Hoc Bonferroni ............................................................................. 37

5.6 Hasil Uji Regresi Linier ....................................................................................... 38

xv

DAFTAR GAMBAR

Gambar Halaman

2.1 Minyak Zaitun ...................................................................................................... 4

2.2 Struktur Kimia Aloksan ...................................................................................... 10

2.3 Mekanisme Peningkatan LDL pada Dislipidemia ............................................... 16

4.1 Tabel Konversi Dosis ........................................................................................... 28

5.1 Grafik Rata-Rata Kadar LDL Tikus Pada Masing-Masing Kelompok ................ 35

5.2 Grafik Linearitas Kadar LDL Dengan Dosis Minyak Zaitun Ekstra Virgin 39

xvi

DAFTAR LAMPIRAN

Gambar Halaman

Lampiran 1: Hasil Penelitian ..................................................................................... 49

Lampiran 2: Analisis Data ......................................................................................... 50

Lampiran 3: Dokumentasi Kegiatan .......................................................................... 52

Lampiran 4: Keterangan Kelaikan Etik ..................................................................... 54

Lampiran 5: Surat Keterangan penelitian .................................................................. 55

xvii

DAFTAR SINGKATAN

ABC-1 : Adenosine triphosphate-binding cassete transporter

ADA : American Diabetes Association

ATP : Adenosine triphosphate

CETP : Cholesterol ester transfer protein

CVD : Cardiovascular Disease

DNA : Deoxyribonucleic acid

EVOO : Extra Virgin Olive Oil

FFA : Free fatty acids

GAD : Glutamic acid decarboxylase

GLUT : Glucose transporters

HDL : High Density Lipoprotein

HLA : Human leucocyte antigens

HUK : Heart UK The Cholesterol Charity

IA-2 : the insulinomia-associated 2 molecule

IAA : Insulin autoantibodies

ICA : Islet cell antibodies

IDF : International Diabetes Federation

IDL : Intermediate density lipoprotein

INSA : Indian National Science Academy

IOC : International Olive Council

ISPAD : International Society for Pediatric and Adolescent Diabetes

LCAT : Lacthin cholesterol acyltransferase

xviii

LDL : Low Density Lipoprotein

LDL-C : LDL cholesterol

LPL : Lipoprotein lipase

LRP : Receptor-related protein

MHC : Major histocompatibility complex

MUFA : Monounsaturated Fatty Acid

NAD : Nicotinamide adenine dinucleotide

PARP : Poly ADP-ribose polymerase

PUFA : Polyunsaturated Fatty Acid

SEPA : Scottish Environmental Protection Agency

SFA : Saturated Fatty Acid

SR-B1 : Scavenger reseptor class B type 1

VLDL : Very Low Density Lipoprotein

WHO : World Health Organization

ZnT-8 : Zinc transporter 8

45

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