KARYA TULIS AKHIR

PENGARUH EKSTRAK BIJI ANGGUR MERAH (Vitis vinifera) TERHADAP

PERBAIKAN HISTOLOGIS SEL BETA PANKREAS TIKUS PUTIH (Rattus novergicus)
STRAIN WISTAR MODEL DIABETIKUM

Oleh:
RAHAYU ENDAH PUSPITA
08020092

UNIVERSITAS MUHAMMADIYAH MALANG

FAKULTAS KEDOKTERAN
2012
 HASIL PENELITIAN

PENGARUH EKSTRAK BIJI ANGGUR MERAH (Vitis vinifera) TERHADAP

PERBAIKAN HISTOLOGIS SEL BETA PANKREAS TIKUS PUTIH (Rattus
novergicus) STRAIN WISTAR MODEL DIABETIKUM

KARYA TULIS AKHIR

Diajukan kepada
Universitas Muhammadiyah Malang
untuk Memenuhi Salah Satu Persyaratan
dalam Menyelesaikan Program Sarjana
Fakultas Kedokteran

Oleh:
RAHAYU ENDAH PUSPITA
08020092

UNIVERSITAS MUHAMMADIYAH MALANG

FAKULTAS KEDOKTERAN
2012

ii
 LEMBAR PENGESAHAAN
LAPORAN HASIL PENELITIAN
Telah disetujui sebagai hasil penelitian
untuk memenuhi persyaratan
Pendidikan Sarjana Fakultas Kedokteran
Universitas Muhammadiyah Malang

Tanggal : 3 Mei 2012

Pembimbing I

dr. Meddy Setiawan, Sp. PD.

Pembimbing II

dr. Sri Adila Nurainiwati, Sp. KK.

Mengetahui,
Fakultas Kedokteran
Dekan,

dr. Irma Suswati, M.Kes.

iii
 LEMBAR PENGUJIAN

Karya Tulis Akhir oleh Rahayu Endah Puspita ini telah diuji dan dipertahankan di
depan Tim Penguji pada tanggal 3 Mei 2012.

Tim Penguji

dr. Meddy Setiawan, Sp.PD , Ketua

dr. Sri Adila Nurainiwati, Sp. KK , Anggota

dr. Hawin Nurdiana, M. Kes , Anggota

iv
 KATA PENGANTAR

Assalamu’alaikum wr. wb

Alhamdulillahirrabil’alamin, segala puji hanya bagi Allah SWT yang telah

memberi petunjuk dan hidayah-Nya sehingga penulis dapat menyelesaikan karya tulis

akhir dengan judul “Efek ekstrak biji anggur merah (Vitis vinifera) terhadap

perbaikan histologis sel beta pankreas tikus putih (Rattus norvegicus) strain wistar

model diabetikum”. Shalawat dan salam senantiasa tercurahkan pada junjungan

Rasulullah Muhammad SAW yang telah membimbing umat manusia dari zaman

gelap menuju jalan yang terang 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 pembimbing I atas dukungan dan

saran yang telah diberikan dalam penyusunan karya tulis akhir ini.

3. dr. Sri Adila Nurainiwati, Sp.KK, selaku pembimbing II atas ketelitian

dalam membimbing demi sempurnanya karya tulis akhir ini.

4. dr. Hawin Nurdiana, M.Kes, selaku penguji atas saran, kritik, dan

bimbingannya.

5. dr. Soebarkah Basoeki, Sp.PA yang telah membantu demi sempurnanya

karya tulis akhir ini.

v
 6. Bu Nurul Mahmudati, Mas Ariesandi beserta staf Laboratorium Kimia

atas segala bantuan yang diberikan.

7. Seluruh staf Tata Usaha dan staf Lab.Terpadu (Pak Yono, Mas Didit, Mas

Faisal, Mas Nyono, Mas Miftah, Pak Joko, Mbak Dila, Mbak Fat, Mbak

Ema, dan Bu Tyas) atas bantuan yang diberikan kepada penulis.

8. Ibunda Dra. Endang Eryani, Ayahanda Pinto, dan Adik-adik atas semua

kasih sayang, dukungan moril dan material, serta do’a yang diberikan.

9. Muhammad Remo Lingga Riesta Armyda yang menjadi sahabat diskusi

dengan sabar memberikan semangat, dukungan, bantuan, kasih sayang,

dan perhatiannya kepada penulis.

10. Sahabat penulis Yosi, Anisa, Dian, Rijal, Handy, Sutami, Faritz, Inneke,

Van serta teman-teman FK angkatan 2008 yang telah banyak memberikan

semangat, do’a dan dukungannya.

11. Semua pihak yang tidak dapat disebutkan satu persatu yang telah

memberikan bantuan dalam penyelesaian penelitian ini.

Penulis menyadari bahwa penulisan ini masih jauh dari kesempurnaan, 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, Mei 2012

Penulis

vi
 ABSTRAK

Endah Puspita, Rahayu. 2012. Efek Ekstrak Biji Anggur Merah (Vitis vinifera)
terhadap Perbaikan Histologis Sel Beta Pankreas Tikus Putih (Rattus
Novergicus) Strain Wistar Model Diabetikum. Tugas Akhir, Fakultas Kedokteran
Universitas Muhammadiyah Malang. Pembimbing: (1) Meddy Setiawan. (2) Sri
Adila Nurainiwati.

Latar Belakang: Pankreas merupakan organ penting dalam mengatur kadar glukosa
darah. Alloxan adalah senyawa diabetogenik yang dapat menghancurkan sel beta
pankreas. Kerusakan sel beta pankreas menyebabkan produksi insulin menurun.
Ekstrak biji anggur merah sebagai penangkal radikal bebas karena mengandung
flavonoid dan OPC. Selain itu OPC juga dapat sebagai proteksi DNA sehingga
memperbaiki sel beta pankreas tikus putih yang rusak.
Tujuan: Membuktikan pengaruh ekstrak biji anggur merah (Vitis vinifera) terhadap
perbaikan histologis sel beta pankreas tikus putih strain wistar model diabetikum.
Metode: Penelitian eksperimental murni, dengan rancangan The Post Test Control
Group Design. Sampel penelitian dibagi menjadi 4 kelompok. Kelompok I (kontrol
negatif), kelompok II (kontrol positif) diberi alloxan,kelompok III diberi alloxan dan
ekstrak biji anggur merah 0,093 gr/200 gr BB/hari, kelompok IV diberi alloxan dan
ekstrak biji anggur merah 0,187 gr/200 gr BB/hari. Dianalisis dengan uji one way
ANOVA, uji korelasi, dan uji regresi.
Hasil penelitian dan diskusi: Hasil uji one way ANOVA terdapat pengaruh yang
bermakna antar kelompok dengan nilai (sig=0,000) p < 0,05. Hasil uji tukey 5%
didapatkan sel beta tiap kelompok berbeda. Hasil uji korelasi didapatkan pearson
correlation=0,907 dengan arah positif artinya semakin besar dosis ekstrak biji anggur
merah maka semakin besar perbaikan sel beta pankreas. Hasil uji regresi didapatkan
R2 = 0,823 yang menunjukkan ekstrak biji anggur berpengaruh terhadap persentase
sel beta sebanyak 82,3%.
Kesimpulan: Ekstrak biji anggur merah (Vitis vinifera) dapat memperbaiki sel beta
pankreas tikus putih (Rattus Novergicus) strain wistar model diabetikum.

Kata kunci: Tikus putih model diabetikum, OPC, Flavonoid, Sel beta pankreas,
Ekstrak biji anggur merah.

vii
 ABSTRACT

Endah Puspita, Rahayu. 2012. The Effect of Red Grape (Vitis vinifera) Seed Extract
to the Histological Improvement of Pancreas Beta Cells in Diabetic Wistar Strain
White Mice (Rattus novergicus) Model.Undergraduate Thesis, Faculty of
Medicine, University of Muhammadiyah Malang. Advisers: (1) Meddy Setiawan.
(2) Sri Adila Nurainiwati.

Background: Pancreas is the vital organ in mantaining blood glucose level. Alloxan
is a diabeogenic compound which is capable of destructing pancreas. The demage of
pancreas beta cell will reduce the insulin production. Red grape seed’s extract can
avoid free radicals because it contains flavonoid and OPC. Meanwhile, OPC can also
be a protection of DNA, that repair the demage of strain wistar pancreas beta cell.
Objective: Provide evidence of red grape (Vitis vinifera) seed extract to the
histological improvement of pancreas beta cells in diabetic wistar strain white mice
(Rattus novergicus) model.
Method: True experimental, with the Post Test Control Group Design. Experiment
samples were split into 4 groups. Group I (negative control), group II (positive
control) was distributed with alloxan, group III was distributed with red grape seed
extract 0,093 gr/200 gr BW/day, group IV was admnistered with red grape seed
extract 0,187 gr/200 gr BW/day. Data was analyzed using one way ANOVA test,
correlation test, and regression test.
Experiment result and discussion: One way ANOVA test performed that there was
a significant influence in different categories (sig=0.000) p<0.05. The result of 5%
tukey test presence that there were beta cell in each. The corellation test resulted the
pearson correlation = 0,907, with positive direction which implied the the greater
doses of red grape seed extract distributed, the higher improvement of pancreas beta
cells would be attained. Regression test resulted R2 = 0.823 which implied that the
red grape seed extract influence 82,3% of beta pankreas cell.
Conslusion: Red grape seed extract (Vitis vinifera) can improve pancreas beta cells
in diabetic wistar strain white mice (Rattus novergicus) model.

Keywords: diabetic white mice model, OPC, Flavonoid, pancreas beta cells, red
grape seed extract.

viii
 DAFTAR ISI

Halaman
JUDUL ............................................................................................................... i
HALAMAN JUDUL.......................................................................................... ii
LEMBAR PENGESAHAN ............................................................................... iii
LEMBAR PENGUJIAN .................................................................................... iv
KATA PENGANTAR ....................................................................................... v
ABSTRAK ......................................................................................................... vii
ABSTRACT ......................................................................................................... viii
DAFTAR ISI ...................................................................................................... ix
DAFTAR TABEL ............................................................................................. xii
DAFTAR GAMBAR ........................................................................................ xiii
DAFTAR SINGKATAN .................................................................................. xiv
DAFTAR LAMPIRAN ...................................................................................... xvi
BAB 1 PENDAHULUAN ................................................................................ 1
1.1 Latar Belakang .................................................................................. 1
1.2 Rumusan Masalah .............................................................................. 3
1.3 Tujuan Penelitian ................................................................................ 3
1.3.1 Tujuan Umum ............................................................................ 3
1.3.2 Tujuan Khusus ........................................................................... 4
1.4 Manfaat Penelitian .............................................................................. 4
1.4.1 Manfaat Akademis ..................................................................... 4
1.4.2 Manfaat Praktis .......................................................................... 4
BAB 2 TINJAUAN PUSTAKA ....................................................................... 5
2.1 Diabetes Melitus ................................................................................. 5
2.1.1 Definisi ................................................................................... 5
2.1.2 Fisiologi insulin normal ........................................................... 5
2.1.3 Patofisiologi diabetes melitus .................................................. 7
2.1.4 Klasifikasi ................................................................................ 11

ix
 2.1.5 Diagnosis .................................................................................. 13
2.1.6 Terapi ........................................................................................ 13
2.2 Pankreas ............................................................................................. 15
2.2.1 Embriologi ................................................................................ 15
2.2.2 Anatomi .................................................................................... 16
2.2.3 Histologi ................................................................................... 18
2.3 Anggur ................................................................................................ 19
2.3.1 Taksonomi .............................................................................. 19
2.3.2 Morfologi ................................................................................ 20
2.3.3 Penyebaran .............................................................................. 21
2.3.4 Biji anggur merah ..................................................................... 22
2.4 Alloxan ............................................................................................... 24
2.4.1 Definisi dan sifat kimia............................................................. 24
2.5 Pengaruh Alloxan Terhadap Kerusakan Sel Beta Pankreas ............... 25
2.6 Pengaruh Ekstrak Biji Anggur Merah Terhadap Kerusakan
Sel Beta Pankreas ............................................................................... 26
BAB 3 KERANGKA KONSEP DAN HIPOTESIS ......................................... 28
3.1 Kerangka Konsep ............................................................................... 28
3.2 Hipotesis .............................................................................................. 30
BAB 4 METODE PENELITIAN....................................................................... 31
4.1 Jenis Penelitian ................................................................................... 31
4.2 Lokasi dan Waktu Penelitian ............................................................. 31
4.3 Populasi dan Replikasi ....................................................................... 31
4.3.1 Populasi ...................................................................................... 31
4.3.2 Replikasi..................................................................................... 31
4.3.3 Besar Replikasi........................................................................... 31
4.3.4 Karakteristik Replikasi Penelitian .............................................. 32
4.3.4.1 Kriteria Inklusi ........................................................................ 32
4.3.4.2 Kriteria Ekslusi........................................................................ 32
4.4 Variabel Penelitian ............................................................................. 33

x
 4.4.1 Variabel bebas ............................................................................ 33
4.4.2 Variabel tergantung .................................................................... 33
4.5 Definisi Operasional ........................................................................... 33
4.6 Alat dan Bahan ................................................................................... 34
4.6.1 Alat ............................................................................................. 34
4.6.2 Bahan.......................................................................................... 34
4.7 Alur Penelitian ................................................................................... 36
4.8 Prosedur Penelitian ............................................................................. 37
4.8.1 Adaptasi Hewan Percobaan ....................................................... 37
4.8.2 Penentuan Dosis ......................................................................... 37
4.8.3 Pembuatan Larutan Alloxan ....................................................... 38
4.8.4 Pembuatan Ekstrak Biji Anggur Merah ..................................... 38
4.8.5 Percobaan ................................................................................... 39
4.9 Analisis Data ...................................................................................... 40
BAB 5 HASIL PENELITIAN DAN ANALISIS DATA .................................. 42
5.1 Hasil Penelitian ................................................................................... 42
5.1.1 Hasil Pengukuran Kadar Glukosa Tikus Putih
(Rattus norvegicus) Strain wistar ........................................... 42
5.1.2 Hasil Perhitungan Jumlah dan Persentase (%) Granula
Sel Beta Pankreas Tikus Putih (Rattus norvegicus)
Strain Wistar............................................................................... 44
5.2 Analisis Data ....................................................................................... 49
BAB 6 PEMBAHASAN .................................................................................... 56
BAB 7 KESIMPULAN DAN SARAN.............................................................. 62
7.1 Kesimpulan ......................................................................................... 62
7.2 Saran.................................................................................................... 62
DAFTAR PUSTAKA ........................................................................................ 64
LAMPIRAN ....................................................................................................... 70

xi
 DAFTAR TABEL

Halaman

Tabel 2.1 Gambaran klinis pasien dengan diabetes melitus tipe I dan II ....... 11

Tabel 2.2 Perbedaan klasifikasi diabetes melitus menurut American

Diabetes Association 1997 dan WHO 1985 ................................... 12

Tabel 4.1 Konversi dosis antar spesies ........................................................... 38

Tabel 5.1 Rerata Kadar Glukosa Darah Tikus Putih

(Rattus norvegicus) Starin Wistar................................................... 43

Tabel 5.2 Rerata Persentase (%) Sel Beta

Pankreas Tikus Putih (Rattus norvegicus) Strain Wistar................ 49

Tabel 5.3 Hasil uji normalitas......................................................................... 50

Tabel 5.4 Hasil uji homogenitas ..................................................................... 50

Tabel 5.5 Hasil uji One Way ANOVA ........................................................... 51

Tabel 5.6 Hasil uji tukey 5% .......................................................................... 51

Tabel 5.7 Resume uji tukey 5% ...................................................................... 52

Tabel 5.8 Hasil uji korelasi ............................................................................. 52

Tabel 5.9 Hasil uji ANOVA regresi ............................................................... 53

Tabel 5.10 Koofesien regresi ............................................................................ 54

xii
 DAFTAR GAMBAR

Halaman

Gambar 2.1 Patogenesis diabetes melitus tipe 2 ............................................. 10

Gambar 2.2 Anatomi pankreas ........................................................................ 18

Gambar 2.3 Histologis pulau langerhan .......................................................... 19

Gambar 2.4 Buah anggur merah ...................................................................... 20

Gambar 2.5 Biji anggur merah ....................................................................... 23

Gambar 2.6 Alloxan ......................................................................................... 24

Gambar 3.1 Skema kerangka konsep .............................................................. 28

Gambar 4.1 Diagram alur penelitian ............................................................... 36

Gambar 5.1 Pulau langerhan kelompok I ........................................................ 45

Gambar 5.2 Pulau langerhan kelompok II ....................................................... 46

Gambar 5.3 Pulau langerhan kelompok III ..................................................... 47

Gambar 5.4 Pulau langerhan kelompok IV ..................................................... 48

Gambar 5.5 Uji regresi sel beta pankreas setelah

pemberian ekstrak biji anggur merah .......................................... 55

xiii
 DAFTAR SINGKATAN

ADA : American Diabetes Association

ADP : Adenosin Di Phospat

ANOVA : Analysis of Variance

ATP : Adenosin Tri Phospat

BB : Berat Badan

C : Celcius

Ca 2+ : Calsium

cAMP : Cyclic Adenosin Monophosphat

CD 4+ : Cluster of differentiation 4

CoQ10 : Coenzym Q10

DMH : Diabetes Melitus Hamil

DNA : Deoxyribonicleic Acid

GAD : Glutamic Acid Decarboxylase

GLUT : Glucose Transporter

HE : Hematoxilin eosin

IFN : Interferon

IL : Interleukin

K+ : Kalium

Kg : Kilogram

MHC : Major Histocompatibility Complex

ml : Mililiter

xiv
mRNA : Messenger Ribonucleic Acid

Nacl : Natrium Chlorida

OHO : Obat Hipoglikemi Oral

OPC : Oligomeric Proanthocyanidin Complex

p : Probability

PERKENI : Perkumpulan Endokrinologi Indonesia

pH : power of Hydrogen

PP : Post Pandrial

ROS : Reactive Oxygen Spesies

SC : Subcutan

SM : Sebelum Masehi

SPSS : Statistical Product and Solution Service

TNF α : Tumor Necrosis Factor alpha

TTGO : Tes Toleransi Glukosa Oral

WHO : World Health Organization

α : Alfa

xv
 DAFTAR LAMPIRAN

Halaman

Lampiran 1 Data pengamatan glukosa darah setelah

pemberian alloxan ......................................................................... 70

Lampiran 2 Data pengamatan glukosa darah setelah

pemberian ekstrak biji anggur ....................................................... 71

Lampiran 3 Data pengamatan preparat pankreas perbesaran 400x .................. 72

Lampiran 4 Foto kegiatan penelitian ................................................................ 75

xvi
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