DAFTAR ISI

HALAMAN SAMPUL.......ii

DAFTAR ISI .....iii

DAFTAR TABEL ..vi

DAFTAR GAMBAR ...vii

DAFTAR SINGKATAN .....viii

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

1.1 Latar Belakang.....1

12 Rumusan Masalah...3

1.3 Tujuan Penelitian .....4

1.4.1 Tujuan Umum...........4

1.4.2 Tujuan Khusus. ........................4

1.4 Manfaat Penelitian .....4

1.4.1 Manfaat Akademis ....4

1.4.2 Manfaat Klinis ....4

BAB II. TINJAUAN PUSTAKA ..6

2.1 Defenisi dan Epidemiologi ........................................................................6

2.2 Etiopatogenesis ..........................................................................................7

2.3 Inflamasi dan Endometriosis ...................................................................10

2.3.1 Teori Inflamasi pada Endometriosis.............................................10

2.3.2 Perubahan imunologi pada endometriosis ...11

2.3.2.1 Sel Natural Killer (NK).14

3
 2.3.2.2 Makrofag...15

2.3.2.3 Sitokin20

2.4 Hormon dan Endometriosis...22

2.5 Peran TNF- pada endometrium ektopik

...................24

2.6 Reaktif Oksigen Spesies dan Ekspresi SOD.25

2.7 Angiogenesis.27

2.7.1 Vascular endothelial growth factor (VEGF) 28

2.7.2 Peran VEGF pada endometrium ektopik..31

2.7.3 Peran steroid ovarium terhadap ekspresi VEGF...32

2.8 Buah Merah ( Pandanus Conoideus Lam)34

2.8.1 Komposisi dan Mekanisme Kerja Komponen Bioaktif

Buah Merah...37

2.8.1.1 Karoten...37

2.8.1.2 Tokoferol39

2.8.1.3 Fenol...41

2.8.1.4 Minyak dan Lemak43

2.9 Tingkat Fertilisasi dan Perkembangan Embrio Mencit yang Diberi

Ekstrak Buah Merah.45

2.10Binatang percobaan pada penelitian endometriosis..46

2.10.1 Tikus sebagai hewan coba.46

BAB III. KERANGKA KONSEP DAN HIPOTESIS PENELITIAN .50

3.1 Kerangka Konsep..50

4
 3.2 Hipotesis Penelitian..52

BAB IV METODE PENELITIAN ..................................................................53

4.1 Desain Penelitian .................................................................................53

4.2 Tempat dan Waktu Penelitian ..............................................................54

4.3 Unit Eksperimen, Replikasi..54

4.3.1 Unit Eksperimen54

4.3.2 Replikasi54

4.4 Kriteria Subyek Penelitian, Variabel Penelitian dan Definisi

Operasional 55

4.4.1 Kriteria Subyek Penelitian.55

4.4.2 Variabel Penelitian.55

4.4.3 Definisi Operasional..55

4.5 Instrumen Penelitian..60

4.6 Prosedur Penelitian61

4.6.1 Prosedur Pengambilan Sampel..61

4.6.2 Tahapan Persiapan Penelitian61

4.7.3 Alur Penelitian..62

4.8 Kerangka Operasional ..64
4.8 Tahapan Pemeriksaan Elisa, Immunohistokimia dan Hispatologi ..65
4.9 Pengelolaan Data..65
4.10Kelayakan Etik 65

DAFTAR PUSTAKA 66

DAFTAR TABEL

5
Tabel 1. Teori patogenesis dan mekanisme endometrium ....................................14

Tabel 2. Kandungan nutrisi dan komponen bioaktif buah merah per 100gr

..45

Tabel 3. Kandungan kultivar lemak pada berbagai kultivar buah merah

...52

Tabel 4. Skala semikuantitatif IRS merupakan hasil perkalian antara skor

persentase sel positif (A) dengan Skor Intensitas reaksi warna (B), jadi

skala IRS = ( A x B )

67

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 DAFTAR GAMBAR

Gambar 1. Teori inflamasi pada patogenesis endometriosis

16

Gambar 2 Teori Hormon : Biosintesis hormon estrogen di jaringan

endometriosis

26

Gambar 3 Skema model NF-kB

31

Gambar 4 Jalur sinyal transduksi TNF

....32

Gambar 5 Jalur Apoptosis

33

Gambar 6 Buah Merah

.44

Gambar 7 Stabilisasi fenol oleh delokasi elektron

...50

Gambar 8 Skema Rancangan Penelitian

61

7
 DAFTAR SINGKATAN

SINGKATAN ARTI DAN KETERANGAN

17-HSD : 17-Beta Hidroksisteorid Dehidrogenase

2H2O :

A : Androestenedion

A20 :

AP : Activator Protein

AFS : American Fertility Society

ASRM : American Society for Reproductive

Medicine

BSA : Bovine Serum Albumin

8
C40H56 : Karotenoid Hidrokarbon

C5H8 :

CA 125 : Cancer Antigen 125

COX : Cyclooxygenase

CMC-NA :

Cu :

DD : Death Domain

DISC : Death Inducing Signaling Complex

DNA :

E1 : Estron

E2 : Estradiol

EGF : Epidermal Growth Factor

ESHREE

FADD : Fas Associated Death Domain

FGF : Fibroblast Growth Factor

FGF- : fibroblast growth factor alpha

FGF- : fibroblast growth factor beta

FIV : Fertilisasi in vitro

FLT :

FSH : Follicle-stimulating Hormone

GDF : Growth Differentiation Factor

9
GnRH : Gonadotropin-releasing Hormone

GV : Germinal vesicle

GVBD : Germinal vesicle breakdown

hSG : human Chorionic Gonadotropin

H2O2 : Hidrogen peroksida

HUVEC : Human Umbilical Vein Endothelial Cells

IAP : Inhibitor protein apoptosis

ICAM-1 : Intracellular Adhesion Molecul-1

ICSI : Intracytoplasmic Sperm Injection

IFN- : Interferon Gamma

IGF : Insulin-like Growth Factor

IL : Interleukin

IB :

IB :

IKK : IB Kinase

IU : International Unit

IRS : Immuno Reactive Score

IKKK : IB kinase kinase

JNK : c-Jun N-terminal kinase

KDR : Kinase Receptor Domain

KIR : Killer Immunoglobulin-like Receptor

KOK : Kompleks Oosit-Kumulus

LD50 :

10
LPS : Lipopolisakarida

MAF : Macrophage Activating Factor

MCP : Monocyte Chemotactic Protein

MDA : Malondialdehyde

MIF : Macrophage migration inhibitory factor

M-DGF : Macrophage-derived Growth Factor

M-CSF : Macrophage Colony Stimulating Factor

mRNA :

MFR : Monthly Fecundity Rate

MRI : Magnetic Resonance Imaging

MEKK : Mitogen-Activated Protein (MAP) Kinase/ERK

Kinase Kinase

MHC : Major Histocompatibility Complex

MMP : Matrix Metalloproteinase

MnSOD :

MT1MMP : Membrane Type-1 Matrix Metalloproteinase

NIK : NF-B Inducing Kinase

NK : Natural Killer

NOS-SCID : Non Obese Diabetic- Severe Combined

Immunodeficient

NSAID : Nonsteroidal anti-Inflammatory

TIMP : Tissue Inhibitor of Metalloproteinase

NF-B : Nuclear Factor Kappa B

11
NIK : NF-B-inducing kinase

NSAID : Nonsteroidal anti-Inflamatory Drug

O2 : Oksida / Oksigen

O2- : Superoksida Anion

OH :

PlGF : Placental Growth Factor

PDGF :

PGF2 :

PGE2 : Prostaglandin Estradiol

PI3K/AKT :

PBS : Phosphate Buffered Saline

PDECGF : platelet-derived endothelial cell growth factor

PKK : Pil Kontrasepsi Kombinasi

PMA : Phorbol myristate acetate

PID : Pelvic inflammatory disease

PMSG : Pregnant Mares Serum Gonadotropin

Rac-1 :

RANTES : Regulated On Activation Normal T

Expressed And Secreted

RIP : Receptor Interacting Protein kinase

ROS : Reactive Oxygen Species

RTK : Receptor Tyrosine Kinase

12
SCID : Severe Combined Immunodeficient

SOD : superoksida dismutase

SMAC : Second Mitochondria-derived Activator of Caspases

TCM : Tissue Culture Medium

TGF : Transforming Growth Factor

TGF- : Transforming Growth Factor - Alpha

TGF- : Transforming Growth Factor - Beta

TH : T- Helper

TIMPs : Tissue Inhibitor of Metalloproteases

TLRs : Toll-like Receptors

TNF : Tumor Necrosis Factor

TNF- : Tumor Necrosis Factor - Alpha

TNF-R1 : Tumor Necrosis Factor Receptor 1

TNF-R2 : Tumor Necrosis Factor Receptor 2

TRADD : Tumor Necrosis Factor Receptor 1 Associated

Death Domain

TRAF : TNF receptor associated factor

VEGF : Vascular Endothelial Growth Factor

VEGFR-1 : Fms-Like Tyrosine Kinase-1

VEGFR-2 : Kinase Insert Domain-Containing Receptor

Fetal Liver Kinase

VEGFR-3 : FLT-4

13
ZnSOD :

14