Post on 24-Feb-2020
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
v
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
xiii
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
DAFTAR PUSTAKA
Adam Jhon M.F, 2009, Dislipidemia, In: Sudoyo A.W, Bambang Setiyohadi, Idrus Alwi, Marcellus Simadibrata K, Siti Setiati, Buku Ajar Ilmu Penyakit Dalam Edisi Kelima Jilid III. Jakarta: Interna Publishing. pp. 1984-1988.
Adiels, M, Olofsson, S.O, Taskinen, M.R, et al, 2008, Metabolic Syndrome and Atherosclerosis, Arterioscler Thromb Vasc Biol. 2008;28:1225-1236.
Alexandru I, 2011, Experimental use of animals in research, Balneo-Research Journal, Vol.2, no.1, pp. 65-69.
American Diabetes Association, 2015, Standards of Medical Care in Diabetes-2015, Journal of Clinical and Applied Research and Education, Vol.38, pp.1-94.
American Family Physician, 2011, Clinical Evidence Handbook, BMJ Publishing Group, London, pp. 1270.
Balitbankes, 2013, Riset Kesehatan Dasar 2013, http://www.litbang.depkes.go.id/, Diakses 22 Maret 2017.
Botham KM, Mayes PA, 2009, Lipid yang Penting Secara Fisiologis, dalam: Murray RK, Granner DK, Rodwell VW, Biokimia Harper, Jakarta: EGC, hal. 128-138.
Brill JB, 2008, The Mediterranean Diet and Your Health, American Journal of Lifestyle Medicine, Sage Publications, Vol.3, pp.44-56.
Budiarto, 2004, Meteodologi Penelitian Kedokteran, Sebuah Pengantar, Jakarta, Penerbit Buku Kedokteran EGC, pp. 134-137.
Carolina E., Joan R. C., Xavier Pintó, 2014, Polyphenol fraction of extra virgin olive oil protects against endothelial dysfunction induced by high glucose and free fatty acids through modulation of nitric oxide and endothelin, Redox Biology, 2, pp 971–977.
Clemente A V, Desai P V, 2012, Hepatoprotective Effects of Amaranthus Tricolor Linn. Extracts on The Alloxan Diabetic RAT (Rattus Norvegicus), International Journal of Biology, Pharmacy and Allied Sciences, Vol.1, pp.594-603.
46
Dixit AK, Dey R, Suresh A, et al, 2014, The Prevalence of Dyslipidemia in Patients with Diabetes Mellitus of Ayurveda Hospital, Journal of Diabetes & Metabolic Disorders, pp.1-6.
Doyle, M.E dan Josephine M.E, 2007, Mechanisms of Action of GLP-1 in the Pancreas, Pharmacol Ther., 113(3), pp. 546-593.
Federer WT, 1991, Statistic and Society: Data Collection and Interpretation, Second Edition, New York: Marcel Dekker.
Flynn M, Wang S. 2015, Olive oil as medicine: the effect on blood lipids and lipoproteins’, UC Davis Olive Center, pp. 1-6.
George K, Alberti M.M, 2010, The Classification and Diagnosis of Diabetes Mellitus, In: Holt R I.G, Cockram C, Flyvbjerg A, Goldstein BJ, Textbook of Diabetes 4th edition, Willey-Blackwell, Singapore, pp.24-30.
Ghanbari, R, Anwar, F, Alkharfy, K.M, Gilani AH, Saari N, 2012, ‘Valuable Nutrients and Functional Bioactives in Different Parts of Olive (Olea europaea L.)’, A Review. Int. J. Mol. Sci 13, pp. 3291-3340.
Haas ME, Attie AD, Biddinger SB, 2013, The Regulation of ApoB Metabolism by Insulin, Division of Endocrinology, Boston Children’s Hospital, Harvard Medical School, Boston Massachusetts, USA, pp.1-16.
Heart UK The Cholesterol Charity, 2015, Cholesterol and Lipoproteins, http://heartuk.org.uk/files/uploads/documents/huk_fs_mfsA_cholesterollipoproteins_v2.pdf, Diakses 8 Juni 2015.
Iakoubov R, Ahmed A, Lauffer LM, 2011, Essential Role for Protein Kinase C in Oleic Acid-Induced Glucagon-Like Peptide-1 Secretion in Vivo in the Rat, Endocrinology, 152, pp.1244 –1252.
INSA (Indian National Science Academy), 2000, Guideline For Care and Use Of Animals In Scientific Research, Bengal Offset Works, New Delhi, pp. 14-15.
International Olive Council, 2013, Designation and Definition of Olive Oils. http://www.internationaloliveoil.org/estaticos/view/83-designations-and-definitions-of-olive-oils. Diakses tanggal 10 Juni 2015.
47
International Society for Pediatric and Adolescent Diabetes, 2011, Diabetes in Childhood and Adolescence, International Diabetes Federation, Australia, pp. 9.
James WH, 2013, LDL Cholesterol Direct Enzymatic Colorimetric Method for In-Vitro Diagnostic, Atlas Medical Vol. 4, pp.1-2.
Kwan B.C.H, Kronenberg F, Beddhu S, et al, 2007, Lipoprotein Metabolism and Lipid Management in Chronic Kidney Disease, J Am Soc Nephrol 18, pp. 1246 –1261.
Lenzen S, 2008, The mechanisms of alloxan- and streptozotocin-induced diabetes, Diabetologia 51, pp.216–226.
Loghmani E, 2005, Diabetes Mellitus: Type 1 and Type 2, Guidelines for Adolescent Nutrition Services, University of Minnesota, pp. 168.
Madigan C, Ryan M, Owens D, 2000, Dietary Unsaturated Fatty Acids in Type 2 Diabetes, Diabetes Care, 23, pp. 1472-1477.
Ozougwu, J.C, Obimba K.C, Belonwu C.D, et al, 2013, The Pathogenesis and Pathophysiology of Type 1 and Type 2 Diabetes Mellitus, Journal of Physiology and Pathophysiology, Vol.4, pp. 46-57.
PERKENI, 2011, Konsensus Pengelolaan dan Pencegahan Diabetes Melitus Tipe 2 di Indonesia 2011, http://www.academia.edu/, Diakses tanggal 30 Mei 2015.
Peuhkuri K, Vapaatalo H, Korpela R, 2010, Even Low-Grade Inflammation Impacts on Small Intestinal Function, World Journal of Gastroenterology, 16(9), pp 1057–1062.
Radenkovic M, Stojanovic M, Prostran M, 2015, Experimental Diabetes Induced By Alloxan And Streptozotocin: The Current State Of The Art,Journal of Pharmacological and Toxicological Methods, 78, pp. 13-31.
Rigacci S., Guidottia V., Bucciantinia M., et al. 2010, Oleuropein aglycon prevents cytotoxic amyloid aggregation of human amylin, Journal of Nutritional Biochemistry, vol 1, no. 21, Apr, pp 726–735.
48
Rohilla A, Shahjad A, 2012. Alloxan Induced Diabetes: Mechanisms and Effects, International Journal of Research in Pharmaceutical and Biomedical Sciences, Vol.3, pp.819-823.
Rui-Li Y, Yong-Hui S, Gang H, , et al. 2008, Increasing Oxidative Stress with Progressive Hyperlipidemiain Human: Relation between Malondialdehyde and Atherogenic Index, J. Clin. Biochem, Nutr. 43, pp 154–158
SEPA (Scottish Environmental Protection Agency), 2009, Burial of Small Quantities of Rodent Carcasses Poisoned on Farmland, National West Policy unit, pp.1-2.
Tripoli E, Giammanco M, Tabacchi G, Di Majo D, Giammanco S, La Guardia M, 2005, The Phenolic Compounds of Olive Oil: Structure, Biological Activity and Beneficial Effects on Human, health. Nutr. Res. Rev. 2005, 18, 98–112.
Wikipedia, 2015, Taksonomi zaitun, http://id.wikipedia.org/wiki/Zaitun. Diakses tanggal 7 Juni 2015.
World Health Organization (WHO), 1999, Definition, diagnosis and classifi cation of diabetes mellitus and its complications, Report of a WHO Consulation, pp. 2-3.
Yusuf S, James R, Haffner S, et al, 2006, The Metabolic Syndrome: Etiology,
Controversies, and Emerging Therapies,
http://www.medscape.org/viewarticle/520665_print, Diakses 6 March 2017.