KARYA TULIS AKHIR
Pengaruh Ekstrak Biji Buah Pinang (Areca Catechu) Terhadap Penurunan Kadar Total Homosistein Plasma Pada Tikus Putih (Rattus Novergicus Strain Wistar) Model Aterosklerosis
Oleh: Raden Surya Purnama (09020142)
FAKULTAS KEDOKTERAN UNIVERSITAS MUHAMMADIYAH MALANG 2013
HASIL PENELITIAN
Pengaruh Ekstrak Biji Buah Pinang (Areca Catechu) Terhadap Penurunan Kadar Total Homosistein Plasma Pada Tikus Putih (Rattus Novergicus Strain Wistar) Model Aterosklerosis
KARYA TULIS AKHIR Diajukan kepada Universitas Muhammadiyah Malang untuk Memenuhi Salah Satu Persyaratan dalam Menyelesaikan Program Sarjana Fakultas Kedokteran
Oleh: Raden Surya Purnama (09020142)
UNIVERSITAS MUHAMMADIYAH MALNG FAKULTAS KEDOKTERAN 2013 ii
LEMBAR PENGESAHAN LAPORAN HASIL PENELITIAN Telah disetujui sebagai hasil penelitian Untuk memenuhi persyaratan Pendidikan Sarjana Fakultas Kedokteran Universitas Muhammadiyah Malang
Tanggal : 3 Juni 2013
Pembimbing I
dr. Meddy Setiawan, Sp.PD
Pembimbing II
dr. Desy Andari
Mengetahui, Fakultas Kedokteran Dekan,
dr. Irma Suswati, M.Kes
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LEMBAR PENGUJIAN
Karya Tulis Akhir oleh Raden Surya Purnama ini telah diuji dan dipertahankan di depan Tim Penguji pada tanggal 3 Juni 2013
Tim Penguji
dr. Meddy Setiawan, Sp.PD
Ketua
dr. Desy Andari
Anggota
dr. Isbandiyah, Sp.PD
Anggota
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KATA PENGANTAR
Assalamu’alaikum wr.wb Puji syukur kehadirat Allah SWT atas segala rahmat dan karunia-Nya sehingga penulis dapat menyelesaikan skripsi yang berjudul “Pengaruh Ekstrak Biji Buah Pinang (Areca Catechu) Terhadap Penurunan Kadar Total Homosistein Plasma Pada Tikus Putih (Rattus Novergicus Strain Wistar) Model Aterosklerosis”. Shalawat dan salam senantiasa tercurahkan pada junjungan Rasulullah Muhammad SAW yang telah membimbing umat manusia dari zaman gelap menuju jalan yang terang benderang yakni agama Islam. Pada penulisan karya tulis akhir ini, penulis banyak mendapat bimbingan dan bantuan dari berbagai pihak. Oleh karena itu dalam kesempatan ini penulis mengucapkan terima kasih yang tak terhingga kepada : 1. dr. Irma Suswati, M.Kes, selaku Dekan Fakultas Kedokteran Universitas Muhammadiyah Malang. 2. dr. Meddy Setiawan, Sp.PD, selaku Pembantu Dekan I Fakultas Kedokteran Universitas Muhammadiyah Malang sekaligus dosen pembimbing I yang telah meluangkan waktu serta banyak memberikan masukan dan dukungan demi kesempurnaan penelitian ini sehingga tugas akhir ini dapat terselesaikan. 3. dr. Fathiyah Safitri, M.Kes, selaku Pembantu Dekan II Fakultas Kedokteran Universitas Muhammadiyah Malang. 4. dr. Iwan Sys Indrawanto, Sp.KJ, selaku Pembantu Dekan III Fakultas Kedokteran Universitas Muhammadiyah Malang.
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5. dr. Desy Andari, selaku dosen pembimbing II yang telah meluangkan waktu serta banyak memberikan masukan dan dukungan demi kesempurnaan penelitian ini sehingga tugas akhir ini dapat terselesaikan. 6. dr. Isbandiyah, Sp.PD, selaku dosen penguji proposal dan tugas akhir yang telah memberi tambahan ilmu dan kritik demi kesempurnaan penelitian ini. 7. Semua pihak yang telah membantu dalam menyelesaikan karya tulis akhir ini, penulis ucapkan terima kasih. Penulis menyadari bahwa penulisan ini masih jauh dari sempurna, oleh karena itu penulis membuka diri untuk segala saran dan kritik yang membangun, serta penulis mengharapkan agar karya tulis akhir ini dapat berguna serta bermanfaat.
Wassalamu’alaikum wr.wb
Malang, Juni 2013
Penulis
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ABSTRAK Purnama, Surya. 2013. Pengaruh ekstrak biji pinang (Areca catechu) terhadap penurunan kadar total homosistein plasma pada tikus putih (Rattus novergicus strain wistar) model aterosklerosis. Karya Tulis Akhir, Fakultas Kedokteran Universitas Muhammadiyah Malang. Pembimbing: (1) Meddy Setiawan*). (2) Desy Andari**). Latar Belakang: Peningkatan kadar total homosistein yang diikuti kadar kolesterol yg tinggi adalah awal dari terjadinya aterosklerosis. Biji pinang dapat digunakan sebagai alternatif terapi dalam menurunkan kadar total homosistein karena kandungan zat antioksidan seperti proantosianidin yang berpotensi sebagai pelindung endotel dari stress oksidatif sehingga homosistein dapat didetoksifikasi secara optimal. Tujuan: Membuktikan adanya pengaruh pemberian ekstrak biji pinang terhadap penurunan kadar total homosistein tikus putih model aterosklerosis. Metode: Menggunakan rancangan pre and post test controlled group dengan sampel penelitian dibagi menjadi 5 kelompok. kelompok I (kontrol negatif), kelompok II (kontrol positif) diberi diet aterogenik dan tinggi protein selama 35 hari, dan tiga kelompok lainnya ditambah dengan pemberian ekstrak biji pinang dengan dosis: 1,8; 2,25; 2,7 mg/ekor/hari selama 1 bulan. Hasil Penelitian: Pemberian diet aterogenik dan tinggi protein selama 35 hari telah meningkatkan kadar total homosistein dengan hasil uji oneway ANOVA sig=0,000 (p<0,05). Pemberian ekstrak biji pinang (1,8; 2,25; 2,7 mg/ekor/hari selama 1 bulan menurunkan kadar total homosistein dengan hasil uji oneway ANOVA sig=0,000 (p<0,05); uji korelasi sig=0,000 (p<0,01) dan uji regresi sig=0,000 (p < 0,01). Penurunan terbanyak pada dosis 2,7 mg/ekor/hari. Diskusi: Ekstrak biji pinang berfungsi sebagai antioksidan mampu melindungi endotel dari stress oksidatif, sehingga endotel akan menghasilkan NO secara optimal. NO akan mendetoksifikasi homosistein dengan jalan berikatan dengan homosistein membentuk SNOHcy. Kesimpulan: Pemberian ekstrak biji pinang menurunkan kadar total homosistein tikus putih model aterosklerosis.
Kata Kunci: Ekstrak biji pinang, kadar total homosistein, tikus strain wistar, aterosklerosis *) : Staff pengajar Ilmu Penyakit Dalam FK UMM **) : Staff pengajar Histologi FK UMM
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ABSTRACT Purnama, Surya. 2013. Effect of betel nut (Areca catechu) extract on lowering total homocysteine level atherosclerosis model of rats (Rattus novergicus wistar strain) . Final Thesis, Medical faculty at University of Muhammadiyah Malang. Supervisor: (1) Meddy Setiawan*). (2) Desy Andari **). Background: Increased levels of total homocysteine followed by high cholesterol levels is the beginning of atherosclerosis. In this case, betel nut may be used as an alternative therapy in lowering levels of total homocysteine because it contains antioxidants such as proanthocyanidin that potentially became endothelial protector of oxidative stress so homocysteine can be optimally detoxified. Purpose: To prove the effect of betel nut extracts on lowering total homocysteine level atherosclerosis model of rats. Metode: Using pre and post test controlled group design with a sample divided into 5 groups. Group I (negative control), group II (positive control) were given a aterogenic and high protein diet for 35 days, and the other three groups combined with betel nut extract dose: 1.8; 2.25, 2.7 mg / head / day for 1 months. Result of research: Administration of aterogenic and high protein diet for 35 days had increased levels of total homocysteine with oneway ANOVA test results sig = 0.000 (p <0,05). Betel nut extract (1.8; 2.25, 2.7 mg / head / day for 1 month had lowered levels of total homocysteine with the result of oneway ANOVA sig=0,000 (p<0,05); correlation test sig=0,000 (p<0,01) and regression test sig=0,000 (p<0,01). Decreased most at dose 2,7 mg/head/day. Discussion: Extract of betel nut act as antioxidants that protect endothelium from oxidative stress, thus endothelial will produce NO optimally. NO will detoxify homocysteine by binding to homocysteine to form SNOHcy. Conclusion: Betel nut extracts lowered total homocysteine level atherosclerosis model of rats.
Key Word: Betel nut extract, total homocysteine, strain wistar rats, atherosclerosis model. * ) : Staff lecturer division of Internal Medicine, Faculty of Medicine, UMM **) : Staff lecturer division of Histology, Faculty of Medicine, UMM
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DAFTAR ISI
JUDUL .........................................................................................................................
i
HALAMAN JUDUL....................................................................................................
ii
LEMBAR PENGESAHAN .........................................................................................
iii
LEMBAR PENGUJIAN ..............................................................................................
iv
KATA PENGANTAR .................................................................................................
v
ABSTRAK ................................................................................................................... vii ABSTRACT ................................................................................................................... viii DAFTAR ISI ................................................................................................................
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DAFTAR TABEL ........................................................................................................ xii DAFTAR GAMBAR ................................................................................................... xiii DAFTAR SINGKATAN ............................................................................................. xiv DAFTAR LAMPIRAN ................................................................................................ xvi BAB I PENDAHULUAN ...........................................................................................
1
1.1 Latar Belakang ...........................................................................................
1
1.2 Rumusan Masalah ......................................................................................
3
1.3 Tujuan Penelitian .......................................................................................
4
1.4 Manfaat Penelitian .....................................................................................
5
BAB II TINJAUAN PUSTAKA .................................................................................
6
2.1 Aterosklerosis .............................................................................................
6
2.1.1 Faktor Resiko Aterosklerosis ......................................................
6
2.1.2 Hipotesis Terjadinya Aterosklerosis ...........................................
7
2.1.3 Klasifikasi Mekanisme Aterosklerosis ........................................
9
2.1.3.1 Cedera Endothel (Endotelial Injury) ............................
9
2.1.3.2 Akumulasi Leukosit ..................................................... 10 2.1.3.3 Pembentukan Foam Cell .............................................. 11
2.2 Homosistein ............................................................................................... 12 2.3 Pinang (A. catechu) .................................................................................... 18 2.3.1 Kandungan Kimia ....................................................................... 21 2.3.2 Proantosianidin............................................................................ 21 2.3.3 Proantosianidin Sebagai Antioksidan ......................................... 24 2.4 Efek Ekstrak Biji Pinang (A. catechu) Terhadap Homosistein .................. 27 BAB III KERANGKA KONSEP DAN HIPOTESA .................................................. 28 3.1 Kerangka Konsep ....................................................................................... 28 3.2 Hipotesa ..................................................................................................... 30 BAB IV METODE PENELITIAN .............................................................................. 31 4.1 Rancangan Penelitian ................................................................................. 31 4.2 Lokasi dan Waktu Penelitian ..................................................................... 31 4.3 Populasi dan Sampel .................................................................................. 31 4.3.1 Populasi ....................................................................................... 31 4.3.2 Sampel ......................................................................................... 31 4.3.3 Estimasi Besar Sampel ................................................................ 31 4.3.4 Teknik Sampling ......................................................................... 33 4.3.5 Karakteristik Sampel Penelitian .................................................. 33 4.3.6 Variabel Penelitian ...................................................................... 33 4.3.6.1 Variabel Bebas ............................................................. 33 4.3.6.2 Variabel Tergantung..................................................... 33 4.3.7 Definisi Operasional.................................................................... 34 4.4 Diet Aterogenik .......................................................................................... 34 4.5 Dasar Penentuan Dosis Buah Pinang ......................................................... 34 4.6 Bahan dan Instrumen Penelitian................................................................. 35 4.7 Prosedur Penelitian..................................................................................... 36 4.7.1 Pembagian Kelompok Tikus ....................................................... 37
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4.7.2 Adaptasi ...................................................................................... 37 4.7.3 Pemberian Diet Aterogenik ......................................................... 38 4.7.4 Pemberian Ekstrak Biji Buah Pinang .......................................... 38 4.8 Sampel Darah ............................................................................................. 39 4.8.1 Reagensia .................................................................................... 39 4.9 Alur Penelitian ........................................................................................... 39 4.10 Analisis Data ............................................................................................ 40 BAB V HASIL PENELITIAN DAN ANALISIS DATA ........................................... 41 BAB VI PEMBAHASAN ............................................................................................ 44 BAB VII KESIMPULAN ............................................................................................ 48 7.1 Kesimpulan ................................................................................................ 48 7.2 Saran ........................................................................................................... 48 DAFTAR PUSTAKA .................................................................................................. 49 LAMPIRAN ................................................................................................................. 53
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DAFTAR TABEL
Tabel 5.1 Kadar Total Homosistein Setelah 35 Hari Pemberian Diet Aterogenik ...... 41 Tabel 5.2 Kadar Total Homosistein Setelah 30 Hari Pemberian Ekstrak Biji Pinang........................................................................................................................... 42
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DAFTAR GAMBAR
2.1 Disfungi Endotel Pada Aterosklerosis ...................................................................
8
2.2 Pembentukan Fatty-Streak Pada Aterosklerosis ....................................................
9
2.3 Patogenesis Terjadinya Aterosklerosis .................................................................. 10 2.4 Proses Terjadinya Aterosklerosis ........................................................................... 11 2.5 Pohon Pinang ......................................................................................................... 18 2.6 Buah Pinang ........................................................................................................... 20 2.7 Mekanisme HDL Sebagai Antioksidan yang Dianalogikan sebagai Proantosianidin .................................................................................................... 26 2.8 Hubungan Nitric Oxide dan Homosistein .............................................................. 27
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DAFTAR SINGKATAN ADP
: Adenosin Di Phosphat
CBS
: Cysthathionine asintase
DNA
: deoxyribose-nucleic acid
ECM
: Extra Cellular Matrix
HDL
: High Density Lipoprotein
IL-1
: Interleukin -1
LDL
: Low Density Lipoprotein
Lp-a
: Lipoprotein a
MCP – 1
: Monocyte chemoatractant protein 1
MTHF
: N-5-methyltetrahydrofolate
MTHFR
: N-5-methyltetrahydrofolate reductase
NO
: Nitric oxide
OPCs
: Oligomeric Proantocyanidins
Ox LDL
: Oxidized LDL
PGI2
: Prostacyclin
PTU
: Propilthiourasil
ROS
: Reactive Oxygen Species
SMC
: Smooth Muscle Cells
TNF-
:Tumour necrosis factor-a
t-PA
: tissue Plasminogen Aktivator
UV
: Ultraviolet
SAH
: S-adenosyl-homocysteine
SAM
: S-adenosyl-methionin vi
VLDL
: Very Low Density Lipoprotein
VCAM-1
: Vascular Cell Adhesion Molecule 1
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DAFTAR LAMPIRAN
LAMPIRAN 1
Hasil Analisis Peningkatan Kadar Total Homosistein Tikus Model Aterosklerosis ....................................................................... 53
LAMPIRAN 2
Hasil Analisis Peningkatan Kadar Total Homosistein Tikus Setelah Perlakuan ............................................................................. 54
LAMPIRAN 3
Dokumentasi.................................................................................... 57
LAMPIRAN 4
Bukti Penelitian ............................................................................... 60
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