KARYA TULIS AKHIR

UJI EFEKTIVITAS EKSTRAK DAUN BIDARA (Ziziphus mauritiana Lam)

TERHADAP KETEBALAN VENTRIKEL KIRI JANTUNG TIKUS PUTIH

(Rattus norvegicus strain wistar) MODEL HIPERTENSI

Oleh:

FIRHAN IKHYANA ZUKRUF

201510330311137

FAKULTAS KEDOKTERAN

UNIVERSITAS MUHAMMADIYAH MALANG

2019

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ii

iv

KATA PENGANTAR

Assalamu‟alaikum Warahmatullah Wabarakatuh

Puji syukur kehadirat Allah Subhanahu wata‟ala Yang Maha Pengasih lagi

Maha Penyayang dan atas karunia-Nya, penulisan tugas akhir ini dapat selesai

dengan baik. Shalawat serta salam selalu tercurahkan kepada Rasulullah

Muhammad shalallahu alaihi wasallam, keluarganya dan para sahabatnya yang

telah berjasa membawa syiar dakwah Islam ke seluruh dunia.

Penelitian tugas akhir ini berjudul “Uji Efektifitas Ekstrak Daun Bidara

(Ziziphus mauritiana Lam.) Terhadap Ketebalan Ventrikel Kiri Pada Tikus Putih

(Rattus Novergicus Strain Wistar) Model Hipertensi”. 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

semua pihak.

Wassalamu‟alaikum Warahmatullah Wabarakatuh

Malang, 12 Mei 2019

Penulis

ix

DAFTAR ISI

LEMBAR PENGESAHAN .................................................................................. i

PERNYATAAN ORISINALITAS ....................................................................... ii

LEMBAR PENGUJIAN ....................................................................................... iii

KATA PENGANTAR ........................................................................................... iv

UCAPAN TERIMAKASIH.................................................................................. v

ABSTRAK ............................................................................................................ vii

ABSTRACT ........................................................................................................... viii

DAFTAR ISI .......................................................................................................... ix

DAFTAR TABEL ................................................................................................. xii

DAFTAR GAMBAR ............................................................................................. xiii

DAFTAR SINGKATAN ....................................................................................... xiv

BAB I 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 ................................................................................. 3

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

1.4.1 Manfaat Ilmu Pengetahuan .............................................................. 3

1.4.2 Manfaat Klinis ................................................................................. 4

1.4.3 Manfaat bagi Masyarakat ................................................................ 4

BAB II TINJAUAN PUSTAKA ........................................................................... 5

2.1 Hipertensi .................................................................................................... 5

2.1.1 Definisi Hipertensi ........................................................................... 5

2.1.2 Klasifikasi ........................................................................................ 6

2.1.3 Epidemiologi .................................................................................... 7

2.1.4 Etiologi ............................................................................................. 7

2.1.5 Patofisiologi ..................................................................................... 9

2.1.6 Sistem Renin Angiotensin ............................................................... 11

2.1.7 Diagnosis Hipertensi ........................................................................ 12

2.1.8 Komplikasi ....................................................................................... 14

2.1.9 Tatalaksana ...................................................................................... 16

2.1.10 Kaptopril........................................................................................... 19

2.2 Jantung ........................................................................................................ 20

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2.2.1 Anatomi Jantung .............................................................................. 20

2.2.2 Fisiologi Siklus Jantung .................................................................... 21

2.2.3 Histologi Otot Jantung ...................................................................... 23

2.2.4 Hipertrofi Ventrikel Kiri ................................................................... 24

2.3 Bidara (Zizizphus mauritiana Lam) ............................................................ 26

2.3.1 Klasifikasi ......................................................................................... 26

2.3.2 Morfologi .......................................................................................... 27

2.3.3 Kandungan ........................................................................................ 28

2.3.4 Manfaat ............................................................................................. 29

2.4 Induksi Hipertensi dengan NaCl + Prednison ............................................. 31

2.4.1 Mekanisme NaCl dalam Induksi Hipertensi ..................................... 31

2.4.2 Mekanisme Prednison dalam Induksi Hipertensi ............................. 34

2.5 Tikus ........................................................................................................... 35

2.6 Tinjauan Keislaman .................................................................................... 37

BAB III KERANGKA KONSEP DAN HIPOTESIS ......................................... 40

3.1 Kerangka Konsep Penelitian ...................................................................... 40

3.2 Hipotesis ..................................................................................................... 43

BAB IV METODOLOGI PENELITIAN ........................................................... 44

4.1 Rancangan Penelitian ................................................................................. 44

4.2 Lokasi dan Waktu Penelitian ...................................................................... 44

4.3 Populasi dan Sampel Penelitian ................................................................. 44

4.3.1 Populasi ............................................................................................. 44

4.3.2 Sampel .............................................................................................. 44

4.3.3 Estimasi Besar Sampel ...................................................................... 44

4.3.4 Karakteristik Sampel Penelitian ........................................................ 45

4.4 Variabel Penelitian dan Definisi Operasional ............................................ 46

4.4.1 Variabel ............................................................................................. 46

4.4.2 Definisi Operasional ......................................................................... 47

4.5 Bahan dan Instrumen Penelitian ................................................................. 48

4.5.1 Bahan Penelitian ............................................................................... 48

4.5.2 Instrumen Penelitian ......................................................................... 48

4.6 Alur Penelitian ............................................................................................ 50

4.7 Prosedur Penelitian ..................................................................................... 51

4.7.1 Persiapan Hewan Coba ..................................................................... 51

4.7.2 Penentuan Dosis Ekstrak Daun Bidara ............................................. 51

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4.7.3 Pembuatan Ekstrak Methanol Daun Bidara ...................................... 51

4.7.4 Penyiapan Dosis Penginduksi dan Kaptopril .................................... 52

4.7.5 Perlakuan Pada Kelompok Tikus ...................................................... 53

4.7.6 Proses Anestesi dan Pembuatan Sediaan Histologi .......................... 54

4.7.7 Pengamatan Hasil ............................................................................. 55

4.8 Analisis Data ............................................................................................... 55

BAB V HASIL PENELITIAN DAN ANALISIS DATA ................................... 57

5.1 Hasil Pengamatan Preparat Ventrikel Kiri Jantung .................................... 57

5.2 Uji Nomalitas Data ...................................................................................... 58

5.3 Uji Homogenitas ......................................................................................... 58

5.4 Uji One Way Anova ..................................................................................... 59

BAB VI PEMBAHASAN HASIL PENELITIAN .............................................. 60

6.1 Pembahasan ................................................................................................. 60

6.2 Keterbatasan Penelitian ............................................................................... 63

BAB VII KESIMPULAN DAN SARAN ............................................................. 64

7.1 Kesimpulan ................................................................................................. 64

7.2 Saran ............................................................................................................ 64

DAFTAR PUSTAKA ............................................................................................ 65

LAMPIRAN ........................................................................................................... 76

xii

DAFTAR TABEL

Tabel 2.1 Klasifikasi Tekanan Darah ...................................................................... 7

Tabel 2.2 Klasifikasi Tumbuhan Bidara ................................................................. 25

Tabel 2.3 Kadar Fitokima Ziziphus mauritiana ...................................................... 28

Tabel 2.4 Parameter Fisiologi Tikus Wistar Jantan Usia 4 Bulan .......................... 36

Tabel 4.1 Tabel Definisi Operasional ..................................................................... 47

Tabel 4.2 Konstanta Konversi Dosis ....................................................................... 53

Tabel 5.1 Hasil Uji One Way Anova ....................................................................... 59

xiii

DAFTAR GAMBAR

Gambar 2.1 Algoritma Diagnosis Hipertensi ......................................................... 14

Gambar 2.2 Algoritma Penanganan Hipertensi ..................................................... 18

Gambar 2.3 Anatomi Jantung ................................................................................ 21

Gambar 2.4 Histologi Otot Jantung ...................................................................... 24

Gambar 2.5 Klasifikasi dari Hipertrofi Ventrikel Kiri ........................................... 25

Gambar 2.6 Bunga, Daun dan Buah dari Zizizphus mauritiana ............................ 27

Gambar 2.7 Kandungan Flavonoid dan Fenolik Total Ekstrak Metanol,

Kloroform dan Heksana Daun Ziziphus mauritiana ......................... 29

Gambar 2.8 Mekanisme Peningkatan NaCl di sentral dan perifer ......................... 31

Gambar 2.9 Jalur Neurohormonal Hipotalamus Na+-aldosteron-EO-Angiotensi II.. 32

Gambar2.10 Mekanisme Glukokortikoid dalam menginduksi terjadinya

Hipertensi ............................................................................................. 34

Gambar 5.1 Hasil Pengamatan Tebal Ventrikel Kiri Jantung Tikus ....................... 57

Gambar 5.2 Grafik Ketebalan Otot Ventrikel Kiri Jantung Putih Jantan ............... 58

xiv

DAFTAR SINGKATAN

ACE : Angiotensin Converting Enzyme

ACE-i : Angiotensin Converting Enzyme inhibitors

ACTH : AdenoCortikoTropin Hormon

ADH : Antidiuretic Hormone

ANG II : Angiotensin II

ARBs : Angiotensin II Receptor Blocker

AT1R : Angiotensin Type 1 Receptor

CHF : Congestive Heart Failure

CNS : Central Nervous System

CSF : Cerebro Spinal Fluid

ENAC : Epithelial Na+ Channels

eNOS : endotheilial Nitric Oxide Synthase

EO : Endogeneous Ouabain

G6P : Glucose 6-Phosphate-Levels

H2O2 : Hidrogen Peroksida

HE : Hematoxilin Eosin

IDH : Isolated Diastolic Hypertension

ISH : Isolated Systolic Hypertension

L-Name : N-nitro-L-arginine-metilester

mmHg : Milimeter Air Raksa

NaCl : Natrium Klorida

NO :Nitrit Oksida

xv

NOS : Nitric Oxide Synthase

OVLT : Organosum Vaskulosum Lamina Terminalis

PVN : Paraventrikular Nucleus

RAAS : Renin Angiotensin Aldosteron System

RAS : Renin Angiotensin System

ROS : Reactive Oxygen Species

SD : Sprague-Dawley

SFO : Sub Fornikal Organ

SON : Supra Optikal Nukleus

SNA : Sympathetic Nerve Activity

SNS : Sympathetic Nervous System

LAMPIRAN

I. Analisis Data

II. Dokumentasi Kegiatan

III. Uji Taksonomi Daun Bidara

IV. Surat Etik Penelitian

V. Surat Keterangan Lolos Komisi Ilmiah

VI. Surat Keterangan Pembacaan Hasil Patologi Anatomi

VII. Surat Keterangan Telah Melakukan Penelitian

VIII. Kartu Konsultasi Tugas Akhir

IX. Hasil Deteksi Plagiasi

65

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