SKRIPSI

DIANI MEGA SARI

PENGARUH PEMBERIAN EKSTRAK

TEMULAWAK(Curcuma xanthorrhiza Roxb.)

SEBAGAI ADJUVAN TERAPI VALSARTAN

TERHADAP HISTOPATOLOGI JANTUNG

PADA MENCIT JANTAN (Mus musculus)

YANG DIINDUKSI HIPERTENSI

PROGRAM STUDI FARMASI

FAKULTAS ILMU KESEHATAN

UNIVERSITAS MUHAMMADIYAH MALANG

2015

ii

Lembar Pengesahan

PENGARUH PEMBERIAN EKSTRAK TEMULAWAK

(Curcuma xanthorrhiza Roxb.) SEBAGAI ADJUVAN TERAPI

VALSARTAN TERHADAP HISTOPATOLOGI JANTUNG

PADA MENCIT JANTAN (Mus musculus)

YANG DIINDUKSI HIPERTENSI

SKRIPSI

Dibuat untuk memenuhi syarat mencapai gelar Sarjana Farmasi pada

Program Studi Farmasi Fakultas Ilmu Kesehatan

Universitas Muhammadiyah Malang

2015

Oleh :

DIANI MEGA SARI

NIM : 201110410311056

Disetujui oleh :

Pembimbing I Pembimbing II

Dra. Lilik Yusetyani, Apt., Sp. FRS dr. Dian Yuliarta Lestari, Sp.PA

NIP . 11407040450 NIP. 11308090462

iii

Lembar Pengujian

PENGARUH PEMBERIAN EKSTRAK TEMULAWAK

(Curcuma xanthorrhiza Roxb.) SEBAGAI ADJUVAN TERAPI

VALSARTAN TERHADAP HISTOPATOLOGI JANTUNG

PADA MENCIT JANTAN (Mus musculus)

YANG DIINDUKSI HIPERTENSI

SKRIPSI

Telah diuji dan dipertahankan di depan tim penguji

Pada tanggal 29 Juli 2015

Oleh :

DIANI MEGA SARI

NIM : 201110410311056

Tim Penguji :

Penguji I Penguji II

Dra. Lilik Yusetyani, Apt., Sp. FRS dr. Dian Yuliarta Lestari, Sp.PA

NIP . 11407040450 NIP. 11308090462

Penguji III Penguji IV

Siti Rofida, S.Si., M.Farm., Apt. Hidajah Rachmawati, S.Si., Apt., Sp.FRS.

NIP. 11408040453 NIP. 11406090449

iv

KATA PENGANTAR

Bismillahirrohmanirrohim

Assalamualaikum warohmatullahi wabaraokatuh

Puji syukur tercurahkan kepada Allah SWT, Tuhan semesta alam karena

berkat rahmat dan hidayahnya, penulis dapat menyelesaikan skripsi yang berjudul

Pengaruh Pemberian Ekstrak Temulawak (Curcuma xanthorrhiza Roxb.)

Sebagai Adjuvan Terapi Valsartan Terhadap Histopatologi Jantung Pada

Mencit Jantan (Mus musculus) Yang Diinduksi Hipertensi.

Skripsi ini diajukan untuk memenuhi persyaratan dalam mencapai gelar

Sarjana Farmasi pada Program Studi Farmasi Fakultas Ilmu Kesehatan

Universitas Muhammadiyah Malang, dalam penyusunan skripsi ini penulis tidak

terlepas dari peranan pembimbing dan bantuan dari seluruh pihak. Oleh karena

itu, dengan segala kerendahan hati, penulis mengucapkan terima kasih kepada:

1. Allah SWT, Tuhan semesta alam yang memberikan rahmat, nikmat dan

hidayahnya kepada umatnya, Rasulullah SAW, yang sudah menuntun kita

menuju jalan yang lurus.

2. Bapak Yoyok Bekti Prasetyo, S.Kep., M.Kep., Sp.Kom selaku Dekan

Fakultas Ilmu Kesehatan Universitas Muhammadiyah Malang yang telah

memberikan kesempatan penulis belajar di Fakultas Ilmu Kesehatan

Universitas Muhammadiyah Malang.

3. Ibu Nailis Syifa’, S.Farm.,M.Sc.,Apt selaku Ketua Program Studi Farmasi

sekaligus Dosen Wali Universitas Muhammadiyah Malang yang telah

memberikan motivasi dan kesempatan penulis belajar di Program Studi

Farmasi Universitas Muhammadiyah Malang.

4. Ibu Dra. Lilik Yusetyani, Apt., Sp. FRS selaku Dosen Pembimbing I, dan

dr. Dian Yuliarta Lestari, Sp.PA selaku Dosen Pembimbing II disela

kesibukan beliau masih bisa meluangkan waktu untuk membimbing dan

memberi pengarahan dan dorongan moril sampai terselesaikannya skripsi

ini.

v

5. Ibu Siti Rofida, S.Si., M.Farm., Apt. dan Ibu Hidajah Rachmawati, S.Si.,

Apt., Sp.FRS selaku Dosen Penguji yang telah banyak memberikan saran

dan masukan serta motivasi demi kesempurnaan skripsi ini.

6. Untuk semua para bapak dan ibu dosen Program Studi Farmasi

Universitas Muhammadiyah Malang, yang telah memberikan waktunya

untuk mengajarkan ilmu-ilmu yang sangat bermanfaat.

7. Ibu Sendy Lia Yunita, S.Farm., Apt yang telah bersusah payah membantu

jalannya ujian skripsi sehingga kami dapat melaksanakan ujian skripsi

dengan baik beserta Staff Tata Usaha Program Studi Farmasi Universitas

Muhammadiyah Malang terima kasih karena telah banyak membantu

dalam hal administrasi.

8. Orang tua tercinta Bapak Budi Irianto,S.H dan Ibu Murlini, S.Pd yang

tiada hentinya memotivasi dalam segala hal, dengan sabar mendoakan

untuk kesuksesan putrinya. Terima kasih banyak atas didikan, kerja keras,

dan kasih sayang yang diberikan.

9. Buat kakak dan adik tersayang (Jarwo Permana Putra, S.E.,Ak. dan Drana

Salsabila) yang memotivasi penulis untuk jadi yang lebih baik lagi.

10. Teman-teman seperjuangan team skripsi ―CURCUMIN‖ Vita, Bela, Putri,

Reny, Opik, Priyadi, Ilham, ka Wawan, ka Mutia, dan anggota lainnya,

terimakasih banyak buat semangat, saran, masukan, bantuan dan

kerjasamanya selama ini. Kalian luar biasa, sedih aja tetap bahagia apalagi

saat bahagia.

11. Buat teman piknik dan seperjuangan Eya, Aisyah, Wildan, Yolla, Lina,

yang selalu senang sedih bersama selama 4 tahun perkuliahan.

12. Teman-teman Farmasi B dan Teman-teman Farmasi 2011 terima kasih

atas kebersamaannya selama 4 tahun terakhir ini.

13. Teman sekamar tersayang Risma Yulita terimakasih atas bantuan saran

dan semangatnya selama 4 tahun.

14. Terimakasih untuk Erik Agashi yang selalu membantu penulis selama di

Malang, tempat untuk cerita senang, sedih, dll. Terimakasih selalu

memberikan semangat dan motivasi selama ini.

vi

15. Untuk semua pihak yang belum disebutkan namanya, penulis mohon maaf

dan terima kasih yang sebesar-besarnya. Semua keberhasilan ini tak luput

dari bantuan, doa yang telah kalian semua berikan.

Jasa dari semua pihak yang telah membantu dalam penelitian ini, penulis

tidak mampu membalas dengan apapun. Semoga amal baik semua pihak

mendapat imbalan dari Allah SWT. Akhir kata penulis berharap semoga

penelitian ini bermanfaat bagi berbagai pihak dan menambah wawasan serta

memperluas pola pikir sebagai seorang farmasis.

Malang,

Peneliti,

Diani Mega Sari

vii

DAFTAR ISI

Halaman

HALAMAN JUDUL .................................................................................. i

LEMBAR PENGESAHAN ....................................................................... ii

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

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

RINGKASAN ............................................................................................ vii

ABSTRAK ................................................................................................. ix

ABSTRACK .............................................................................................. x

DAFTAR ISI .............................................................................................. xi

DAFTAR TABEL ...................................................................................... xiv

DAFTAR GAMBAR ................................................................................. xv

DAFTAR LAMPIRAN .............................................................................. xvi

DAFTAR SINGKATAN ........................................................................... xvii

BAB I PENDAHULUAN ...................................................................... 1

1.1 Latar belakang ........................................................................ 1

1.2 Rumusan Masalah .................................................................. 4

1.3 Tujuan Penelitian ................................................................... 4

1.4 Manfaat Penelitian ................................................................. 4

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

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

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

2.1.2 Epidemiologi Hipertensi ................................................. 5

2.1.3 Etiologi Hipertensi ......................................................... 6

2.1.3.1 Hipertensi Essensial ........................................... 6

2.1.3.2 Hipertensi Sekunder ........................................... 6

2.1.4 Manifestasi Klinik Hipertensi ......................................... 7

2.1.5 Klasifikasi dan Kriteria Hipertensi .................................. 7

2.1.6 Patofisiologi Hipertensi ................................................... 8

2.1.7 Komplikasi Hipertensi .................................................... 11

2.2 Tinjauan Jantung ..................................................................... 12

2.2.1 Anatomi dan Fisiologi Jantung ....................................... 12

viii

2.3 Hubungan antara Hipertrofi dengan Histologi Jantung ......... 14

2.3.1 Patofisiologi ................................................................... 14

2.3.2 Histologi Jantung ............................................................ 16

2.4. Penatalaksanaan Terapi pada Hipertensi .............................. 18

2.4.1Terapi Non Farmakologi ................................................. 18

2.4.2 Terapi Farmakologi ........................................................ 18

2.4.3 Tinjauan Valsartan ......................................................... 21

2.5 Obat Tradisional ..................................................................... 23

2.6 Tinjauan Temulawak .............................................................. 25

2.6.1 Klasifikasi........................................................................ 26

2.6.2 Kandungan Kimia .......................................................... 26

2.6.3 Curcumin ........................................................................ 26

2.6.3.1 Sifat Kimia dan Stabilitas .................................. 27

2.6.3.2 Khasiat dan Manfaat Curcumin ......................... 28

2.7 Metode Ekstraksi ................................................................... 29

2.7.1 Pelarut ............................................................................. 30

2.7.2 Etanol ............................................................................. 31

2.7.3 Kromatografi .................................................................. 31

2.8 Penginduksi L-NAME ............................................................ 31

2.9 Hewan Coba Mencit .............................................................. 33

2.9.1 Klasifikasi Hewan Coba ................................................. 33

2.9.2 Karakteristik ................................................................... 34

BAB III KERANGKA KONSEPTUAL ................................................ 36

3.1 Kerangka Konseptual .............................................................. 36

3.2 Penjelasan Kerangka Konseptual ........................................... 37

3.3 Hipotesis ................................................................................ 38

BAB IV METODE PENELITIAN ........................................................... 39

4.1 Rancangan Penelitian .............................................................. 39

4.1.1 Jenis Penelitian ................................................................ 39

4.1.2 Jumlah Sampel ................................................................ 39

4.2 Variabel Penelitian .................................................................. 40

4.2.1 Klasifikasi Variabel ......................................................... 40

ix

4.2.2 Definisi Operasional Variabel ......................................... 40

4.3 Tempat dan Waktu Penelitian ................................................. 42

4.4 Subyek Penelitian.................................................................... 42

4.4.1 Kriteria Inklusi ................................................................ 43

4.4.2 Kriteria Eksklusi .............................................................. 43

4.5 Prosedur Penelitian ................................................................ 43

4.5.1 Pembuatan Ekstrak Temulawak ..................................... 43

4.5.2 Penginduksi Hipertensi ................................................... 45

4.5.3 Pemberian Terapi ........................................................... 45

4.5.4 Pembuatan Preparat Histopatologi Organ Jantung ......... 45

4.5.5 Pengamatan Preparat Histopatologi Organ Jantung ....... 45

4.6 Alat dan Bahan ........................................................................ 46

4.6.1 Alat ................................................................................. 46

4.6.2 Bahan .............................................................................. 46

4.7 Alur Penelitian ........................................................................ 47

4.8 Analisis Data .......................................................................... 47

BAB V HASIL PENELITIAN ................................................................ 49

5.1 Hasil Penelitian ...................................................................... 49

5.1.1 Massa Otot Jantung Mencit Jantan (Mus musculus) ...... 49

5.1.2 Ketebalan Ventrikel Kiri ................................................ 50

5.2 Analisis Data .......................................................................... 52

5.2.1 Uji Normalitas ................................................................ 52

5.2.2 Uji Homogenitas ............................................................ 53

5.2.3 Uji One Way Anova ........................................................ 53

5.2.4 Uji Post Hoc LSD .......................................................... 54

5.2.5 Uji Pearson Correlation ................................................ 54

BAB VI PEMBAHASAN HASIL PENELITIAN ................................. 55

BAB VII KESIMPULAN DAN SARAN ................................................ 60

7.1 Kesimpulan ............................................................................ 60

7.2 Saran ...................................................................................... 60

DAFTAR PUSTAKA ................................................................................. 61

LAMPIRAN ................................................................................................ 68

x

DAFTAR TABEL

Tabel II.1 Klasifikasi Tekanan Darah ......................................................... 8

Tabel II.2 Profil farmakokinetik golongan obat ARB ............................... 20

Tabel II.3 Karakteristik Mus musculus ....................................................... 34

Tabel V.1 Hasil Penimbangan .................................................................... 49

Tabel V.2 Hasil Ketebalan Ventrikel Kiri .................................................. 50

Tabel V.3 Uji Normalitas Shapiro-Wilk ..................................................... 53

Tabel V.4 Uji Homogenitas Levene Test ................................................... 53

Tabel V.5 Uji Pearson Correlation ........................................................... 54

xi

DAFTAR GAMBAR

Gambar 2.1 Perbedaan efek stimulasi reseptor AT1dan AT2 ................... 9

Gambar 2.2 Renin-angiotensin-aldosterone system .................................. 11

Gambar 2.3 Struktur jantung dan Sirkulasi Darah pada Jantung ............... 13

Gambar 2.4 Sinyal utama dan mediator umum renovasi kardiomiosit .... 16

Gambar 2.5 Patologi hypertrophic cardiomyopathy ................................ 17

Gambar 2.6 Ketebalan Otot Jantung Bagian Ventrikel Kiri ..................... 18

Gambar 2.7 Kerja obat pada sistem renin-angiotensin-aldosteron ........... 22

Gambar 2.8 Struktur Kimia Valsartan ...................................................... 22

Gambar 2.9 Tanaman Temulawak ............................................................ 25

Gambar 2.10 Struktur kimia Curcuminoid ................................................ 27

Gambar 2.11 Curcumin menghambat aktivitas p300 HAT ....................... 29

Gambar 2.12 Mekanisme L-NAME induksi Hipertensi ............................ 32

Gambar 2.13 Mus musculus ....................................................................... 33

Gambar 3.1 Kerangka Konsep .................................................................. 36

Gambar 4.1 Rancangan Penelitian ............................................................ 39

Gambar 4.2 Diagram alir ekstraksi kurkumin .......................................... 44

Gambar 4.3 Alur Skema Penelitian .......................................................... 47

Gambar 5.1 Grafik Rata-Rata Massa Otot Jantung .................................. 50

Gambar 5.2 Grafik Rata-Rata Ketebalan Ventrikel Kiri .......................... 51

Gambar 5.3 Ketebalan Ventrikel Kiri ....................................................... 52

xii

DAFTAR LAMPIRAN

Lampiran Halaman

1. Daftar Riwayat Hidup ............................................................................. 68

2. Perhitungan Dosis dan Preparasi Sediaan ............................................... 69

3. Surat Determinasi Temulawak ............................................................... 71

4. Surat Keterangan Kelaikan Etik ............................................................. 72

5. Surat Keterangan Pembacaan Patologi Anatomi .................................... 73

6. Surat Pernyataan ..................................................................................... 74

7. Analisis Statistika ................................................................................... 75

8. Dokumentasi Penelitian ......................................................................... 77

xiii

DAFTAR SINGKATAN

ACE = Angiotensin Converting Enzim

ANG II = Angiotensin II

ARB = Angiotensin Renin Blocker

AT1-R = Angiotensin II Receptor Type 1

AT2-R = Angiotensin II Receptor Type 2

BP = Blood Pressure

cAMP = Cyclic Adenosine Monophosphate

CHF = Chronic heart failure

CO = Cardoac Output

CVD = Cardiovarcular Disease

DASH = Dietary Approaches to Stop Hypertension ERK = Extracellular Regulated Kinase

ESH = European Society of Hypertension

HAT = Histone Asetyltransferase

HCM = Hypertrophyc Cardiomyophaty

HE = Hematoxylin Eosin HF = Heart Failure

HHD = Hypertension Heart Disease

IGF-1 = Insulin Growth Factor type 1

IL-1 = Interleukin-1

IL-6 = Interleukin-2

JNC = Joint National Comittee

JNK = c-Jun N-terminal kinase

L-Name = Nω-nitro-L-arginine methyl ester

LV = Left Ventricle

LVH = Left Ventricle Hypertrophy

MAPK = Mitogen Activated Protein Kinases

M-TOR = Mammalian Target of Rapamycin

NADH = Nicotinamida Adenin Dinukleotida Hydrogen

NADPH = Nicotinamida Adenin Dinukleotida Phosphate

NFAT = Nuclear Factor of Activated T cell

Nf-kB = Nuclear factor-kappaB

NO = Nitric Oxide

NOS = Nitrous Oxide System

P13-akt/PKB = Phosphatidylinositol 3 kinase-aktivasi PKC = Protein Kinase C

RAAS = Renin-Angiotensin Aldosterone System

ROS = Reactive Oxygen Species

SV = Stroke Volume

SVR = Systemic Vascular Resisten

TGF-β = Transforming Growth Factor-β

TNF-α = Tumor Necrosis Factor- α

WHO = World Health Organization

xiv

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