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KARYA TULIS AKHIR
PENGARUH PEMBERIAN EKSTRAK BIJI ANGGUR MERAH
(Vitis vinifera L.) TERHADAP GAMBARAN HISTOPATOLOGI SEL
HEPAR TIKUS PUTIH JANTAN (Rattus novergicus strain wistar) YANG
DIINDUKSI ALKOHOL
Oleh :
DEA SARASWATI
201110330311070
UNIVERSITAS MUHAMMADIYAH MALANG
FAKULTAS KEDOKTERAN
2015
KARYA TULIS AKHIR
PENGARUH PEMBERIAN EKSTRAK BIJI ANGGUR MERAH
(Vitis vinifera L.) TERHADAP GAMBARAN HISTOPATOLOGI SEL
HEPAR TIKUS PUTIH JANTAN (Rattus novergicus strain wistar) YANG
DIINDUKSI ALKOHOL
Diajukan kepada
Universitas Muhammadiyah Malang
Untuk Memenuhi Salah Satu Persyaratan
Dalam Menyelesaikan Program Sarjana
Fakultas Kedokteran
Oleh :
DEA SARASWATI
201110330311070
UNIVERSITAS MUHAMMADIYAH MALANG
FAKULTAS KEDOKTERRAN
2015
vi
KATA PENGANTAR
Assalammu’alaikum Wr. Wb.
Alhamdulillahirrabil’alamin, segala puji bagi Allah SWT yang telah memberi
petunjuk dan hidayah-Nya, shalawat serta salam terlimpahkan kepada Nabi
Muhammad SAW, sehingga penulis dapat menyelesaikan karya tulis akhir dengan
judul “Pengaruh Ekstrak Biji Anggur Merah (Vitis vinifera L.) Terhadap
Gambaran Histopatologi Sel Hepar Tikus Putih Jantan (Rattus norvegicus
strain wistar) Yang Diinduksi Alkohol”.
Dalam penyelesaian karya tulis akhir ini penulis ingin mengucapkan terima
kasih kepada :
1. dr. Irma Suswati, M.Kes, selaku Dekan Fakultas Kedokteran Universitas
Muhammadiyah Malang atas ilmu dan bimbingannya selama di Fakultas
Kedokteran UMM.
2. dr. Moch. Ma’roef, Sp.OG, selaku Pembantu Dekan I Fakultas Kedokteran
UMM atas kesediaan waktu dan penyampaian ilmu yang sangat bermanfaat
bagi masa depan para mahasiswa FK UMM.
3. dr. Rahayu, Sp.S, selaku Pembantu dekan II Fakultas Kedokteran UMM
yang senantiasa bersabar dalam membimbing dan mengajarkan ilmunya
kepada kami.
4. dr. Iwan Sys Indrawanto, Sp.KJ selaku Pembantu Dekan III, yang penuh
semangat dalam menyampaikan ilmu dan motivasi yang membangun
semangat kami selama menjalani pendidikan di Fakultas Kedokteran.
vii
5. dr. Isbandiyah, Sp.PD, selaku pembimbing 1, atas kesabaran, kebaikan hati,
serta kesediaan dalam meluangkan waktu dalam membimbing hingga dapat
menyelesaikan penelitian ini dengan baik.
6. dr. Dian Yuliartha Lestari, Sp.PA, selaku pembimbing 2, atas kesabaran,
kebaikan hati, serta kesediaan dalam meluangkan waktu dalam
membimbing penulis serta membantu dalam proses pengamatan hasil
penelitian hingga dapat menyelesaikan penelitian ini dengan baik.
7. dr. Bragastio Sidharta, Sp.M, selaku penguji tugas akhir ini, atas segala
masukan dan arahan yang sangat bermanfaat dalam pengerjaan tugas akhir
ini dan kesediaan waktu, sehingga tugas ini dapat diselesaikan dengan baik.
8. Ayah dan Ibu, atas doa dan lelah yang diberikan dari pagi hingga pagi lagi,
serta dukungan moril dan materil yang tak pernah putus agar tugas ini dapat
selesai dengan baik. Kak Reza, Kak Dila, Adek Dinda, Ana, Mas Adetya
dan Rani terimakasih sudah menjadi kakak dan adik terbaik serta
penyemangat bagi penulis.
9. Seluruh staf TU dan laboran FK UMM, Mas Miftah dan Pak Joko yang
bersedia membantu setiap tahapan proses penelitian hingga penyelesaian
tugas akhir ini.
10. Sejawat FK UMM angkatan 2011, Adorables, atas dukungan, bantuan, dan
kerjasamanya. Semoga kelak dapat menjadi dokter-dokter profesional yang
barokah, sukses dunia akhirat, dan senantiasa dalam ketaatan kepada Allah
SWT.
11. Sahabat seperjuangan “Grup Biji Anggur Merah” Ayu Desi dan Linda.
viii
12. Sahabat-sahabat terbaik yang menjadi keluarga selama di Malang, Winda,
Erfian, Tari, Jeanny, Lilly, Muqsit, Azilu, Laksita, dan Yuni terimakasih
atas kebersamaan yang sederhana, bantuan, kesabaran, motivasi, dukungan,
dan semua yang telah diberikan.
13. Semua pihak yang terlibat secara langsung maupun tidak langsung,
terimakasih atas bantuan dan dukungannya.
Penulis menyadari bahwa tugas akhir ini masih jauh dari kata
sempurna. Oleh karena itu, penulis sangat mengharapkan saran dan
masukan yang membangun. Dengan mengharapkan Keridhaan-Nya, semoga
karya tulis ini dapat menambah wawasan keilmuan dan bermanfaat bagi
semua pihak.
Wassalammu’alaikum Wr. Wb
Malang, 4 November 2015
Penulis
ix
DAFTAR ISI
JUDUL ............................................................................................................ i
LEMBAR PENGESAHAN ............................................................................ ii
LEMBAR PENGUJIAN ................................................................................. iii
KATA PENGANTAR ..................................................................................... iv
ABSTRAK ...................................................................................................... vii
DAFTAR ISI .................................................................................................... ix
DAFTAR TABEL ............................................................................................ xiii
DAFTAR GAMBAR ....................................................................................... xiv
DAFTAR SINGKATAN ................................................................................ xv
DAFTAR LAMPIRAN ................................................................................... xvi
BAB 1 PENDAHULUAN ............................................................................. 1
1.1 Latar Belakang .............................................................................. 1
1.2 Rumusan Masalah ......................................................................... 3
1.3 Tujuan Penelitian .......................................................................... 4
1.3.1 Tujuan umum ....................................................................... 4
1.3.2 Tujuan khusus ...................................................................... 4
1.4 Manfaat Penelitian ........................................................................ 4
1.4.1 Manfaat ilmu pengetahuan .................................................... 4
1.4.2 Manfaat klinis........................................................................ 5
1.4.3 Manfaat bagi masyarakat ..................................................... 5
BAB 2 TINJAUAN PUSTAKA .................................................................... 6
2.1 Anggur Merah ................................................................................ 6
x
2.1.1 Taksonomi ............................................................................ 6
2.1.2 Morfologi tanaman anggur merah ........................................ 7
2.1.3 Jenis-jenis anggur di Indonesia ............................................. 7
2.1.4 Manfaat buah anggur ............................................................ 8
2.1.5 Proanthocyanidin .................................................................. 9
2.2 Alkohol .......................................................................................... 10
2.2.1 Definisi ................................................................................. 10
2.2.2 Farmakokinetik ................................................................... 12
2.3 Hepar ............................................................................................. 16
2.3.1 Anatomi Hepar ..................................................................... 16
2.3.2 Fisiologi Hepar .................................................................... 18
2.3.3 Histologi Hepar .................................................................... 19
2.4 Penyakit Hati Alkoholik ................................................................ 23
2.4.1 Definisi ................................................................................. 23
2.4.2 Patogenesis ........................................................................... 24
2.4.3 Tanda dan gejala ................................................................... 28
2.4.4 Gambaran histopatologi ........................................................ 29
BAB 3 KERANGKA KONSEPTUAL DAN HIPOTESIS PENELITIAN 33
3.1 Kerangka Konseptual Penelitian ................................................... 33
3.2 Hipotesis Penelitian ........................................................................ 36
BAB 4 METODE PENELITIAN .................................................................. 37
4.1 Rancangan Penelitian .................................................................... 37
4.2 Tempat dan Waktu Penelitian ....................................................... 37
xi
4.3 Populasi dan Sampel Penelitian .................................................... 37
4.3.1 Populasi ................................................................................ 37
4.3.2 Sampel .................................................................................. 37
4.3.3 Estimasi besar sampel .......................................................... 37
4.3.4 Teknik pengambilan sampel ................................................. 39
4.3.5 Karateristik sampel penelitian ............................................... 39
4.4 Variabel dan Definisi Operasional ............................................... 39
4.4.1 Variabel ................................................................................. 39
4.4.2 Definisi Operasional Variabel ............................................ 39
4.5 Alat dan Bahan Penelitian ............................................................ 41
4.5.1 Alat penelitian ...................................................................... 41
4.5.2 Bahan penelitian .................................................................. 42
4.6 Alur Penelitian .............................................................................. 43
4.7 Prosedur Penelitian ....................................................................... 44
4.7.1 Pembagian kelompok tikus .................................................. 44
4.7.2 Proses adaptasi ..................................................................... 44
4.7.3 Penentuan dosis ekstrak biji anggur (Vitis vinifera L.) ........ 44
4.7.4 Penentuan dosis dan pengenceran alkohol .......................... 45
4.7.5 Pemaparan alkohol .............................................................. 46
4.7.6 Proses anestesi dan pembedahan hewan coba ...................... 46
4.7.7 Pembuatan sediaan histologi ................................................ 47
4.7.8 Pengamatan hasil .................................................................. 48
4.7.9 Penguburan tikus percobaan ............................................... 49
xii
4.7.10 Analisis data ........................................................................ 49
BAB 5 HASIL PENELITIAN DAN ANALISA DATA .............................
5.1 Hasil Penelitian ............................................................................ 51
5.1.1 Hasil perhitungan jumlah sel yang membengkak ............... 41
5.2 Analisa Data ................................................................................. 56
BAB 6 PEMBAHASAN ................................................................................ 61
BAB 7 KESIMPULAN ................................................................................. 67
7.1 Kesimpulan ................................................................................... 67
7.2 Saran ............................................................................................. 67
DAFTAR PUSTAKA .................................................................................... 69
LAMPIRAN .................................................................................................. 75
xiii
DAFTAR TABEL
Tabel Halaman
2.1 Kandungan gizi buah anggur ................................................................... 8
2.2 Jenis-jenis minuman beralkohol sesuai kadar alkoholnya ....................... 12
5.1 Jumlah hepar yang membengkak ............................................................. 51
5.2 Hasil analisis data dengan uji one way ANOVA ..................................... 56
5.3 Tabel notasi berdasarkan uji tukey .......................................................... 57
5.4 Hasil analisis data dengan uji korelasi ..................................................... 58
xiv
DAFTAR GAMBAR
Gambar Halaman
2.1 Buah anggur merah ................................................................................... 7
2.2 Metabolisme alkohol ................................................................................ 15
2.3 Anatomi hepar ........................................................................................... 18
2.4 Histologi hepar ......................................................................................... 21
2.5 Gambaran mikroskopik sel hepar ............................................................ 22
2.6 Penyakit hati alkoholik ............................................................................ 23
2.7 Patogenesis penyakit hati alkoholik ......................................................... 25
2.8 Histopatologi penyakit hati alkoholik ...................................................... 29
3.1 Skema kerangka konsep ........................................................................... 33
4.1 Diagram alur penelitian ............................................................................ 43
5.1 Tomografik hasil penelitian ..................................................................... 53
5.2 Gambaran mikroskopis kelompok 1 ........................................................ 53
5.3 Gambaran mikroskopis kelompok 2 ........................................................ 54
5.4 Gambaran mikroskopis kelompok 3 ........................................................ 54
5.5 Gambaran mikroskopis kelompok 4 ........................................................ 55
5.6 Gambaran mikroskopis kelompok 5 ........................................................ 55
5.7 Kurva regresi sel hepar yang membengkak ............................................. 59
xv
DAFTAR SINGKATAN
ADH : Alcohol dehydrogenase
ALD : Alcoholic Liver Disease
CYP2E1 : Cytochrome P450, Family 2, Subfamily E, Polypeptide
EGF : Epidermal Growth Factor
GSH : Gluthathion Sulfur Hidroksil
HDL : High Density Lipoprotein
HGF : Hepatocyte Growth Factor
IL-1 : Interleukin-1
IL-6 : Interleukin-6
IL-8 : Interleukin-8
IL-10 : Interleukin-10
LPS : Lipopolysaccharide
MCP-1 : Monosit Chemotactic Protein1
MDA-LDL : Malondiadelhida-Modified-LDL
MEOS : Microsomal Ethanol-0xidizing System
MTP : Mitochondrial Transition Pore
NAD : Nicotamide Adenine Dinucleotide
NADH : Nicotamide Adenine Dinucleotide (Reduced Form)
OPC : Oligomeric Proanthocyanidins
PDGF : Platelet-Derived Growth
PPAR - α : Peroxisome-Proliferator–Activated Receptor α
ROS : Reactive Oxygen Species
SPSS : Statistical Product and Service Solutions
SREBP - 1c : Sterol Regulatory Element-Binding Protein 1c
TGF-β : Transforming Growth Factor β
TLR 4 : Toll-Like Receptor 4
TNF-α : Tumor Necrosis Factor Alpha
TNF-R1 : Tumor Necrosis Factor - Receptor 1
VLDL : Very low-density lipoprotein
xvi
DAFTAR LAMPIRAN
Lampiran 1 : Hasil Pengamatan ......................................................................... 75
Lampiran 1 : Hasil Analisis data ........................................................................ 76
Lampiran 2 : Dokumentasi Penelitian ................................................................ 82
Lampiran 3 : Determinasi Tanaman Biji Anggur Merah ................................... 83
Lampiran 4 : Surat Keterangan Ektrak Biji Anggur Merah ............................... 84
Lampiran 5 : Surat Keterangan Penelitian ......................................................... 85
Lampiran 6 : Surat Keterangan Kelaikan Etik ................................................... 86
69
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