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HASIL PENELITIAN PENGARUH EKSTRAK JINTAN HITAM (Nigella Sativa) TOPIKAL TETES MATA TERHADAP PENURUNAN EKSPRESI Nuclear Factor Kappa Beta (NF-Kβ) PADA KORNEA TIKUS JANTAN (Rattus Novergicus Strain Wistar) MODEL INFLAMASI Oleh: IMANIYAH HUSNI 201110330311151 UNIVERSITAS MUHAMMADIYAH MALANG FAKULTAS KEDOKTERAN 2015

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Page 1: PENGARUH EKSTRAK JINTAN HITAM ( ) TOPIKAL TETES MATA ... · PDF filehasil penelitian pengaruh ekstrak jintan hitam (nigella sativa) topikal tetes mata terhadap penurunan ekspresi nuclear

HASIL PENELITIAN

PENGARUH EKSTRAK JINTAN HITAM (Nigella Sativa) TOPIKAL

TETES MATA TERHADAP PENURUNAN EKSPRESI Nuclear Factor

Kappa Beta (NF-Kβ) PADA KORNEA TIKUS JANTAN (Rattus Novergicus

Strain Wistar) MODEL INFLAMASI

Oleh:

IMANIYAH HUSNI

201110330311151

UNIVERSITAS MUHAMMADIYAH MALANG

FAKULTAS KEDOKTERAN

2015

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KATA PENGANTAR

Puji syukur kehadirat Allah SWT atas rahmat dan inayah-Nya sehingga

penulis diberi kekuatan dan kemampuan dalam menyelesaikan karya tulis akhir

ini yang berjudul “PENGARUH EKSTRAK JINTAN HITAM (Nigella Sativa)

TOPIKAL TETES MATA TERHADAP PENURUNAN EKSPRESI Nuclear

Factor Kappa Beta (NF-Kβ) PADA KORNEA TIKUS JANTAN (Rattus

Novergicus Strain Wistar) MODEL INFLAMASI”. Karya tulis akhir ini diajukan

untuk memenuhi persyaratan Pendidikan Sarjana Fakultas Kedokteran Universitas

Muhammadiyah Malang.

Pada kesempatan ini, penulis ingin menyampaikan terimakasih kepada :

1. dr. Irma Suswati, M.Kes beserta para pembantu dekan selaku Dewan

Dekanat Fakultas Kedokteran UMM.

2. dr. Bragastio Sidharta, Sp.M, selaku pembimbing 1 atas kesabaran,

kebaikan hati serta kesediaan dalam meluangkan waktu dalam membantu,

membimbing dan mengarahkan penulis dalam menyelesaikan karya tulis

akhir ini.

3. dr. Thontowi Djauhari, NS, M.Kes, selaku pembimbing 2 atas kesabaran,

kebaikan hati serta kesediaan dalam meluangkan waktu dalam membimbing

penulis hingga dapat menyelesaikan menyelesaikan dengan baik.

4. dr. Heru Priyo Husodo, Sp.Rad, selaku penguji tugas akhir ini yang telah

membantu dan memberikan masukan kepada penulis dalam menyelesaikan

karya tulis akhir ini.

5. Seluruh dosen beserta karyawan-karyawati Fakultas Kedokteran UMM yang

selalu membantu dan membimbing penulis.

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6. Kedua orang tua penulis, Ayahanda Husni Husain Hasan dan Ibunda

Djasna Ali atas doa dan dukungannya yang tak pernah putus. Kedua saudari

penulis Inayati Husni dan Amaliyah Husni atas bantuan doa, motivasi dan

tenaganya beserta seluruh keluarga tercinta yang senantiasa setia

mendukung penulis dalam menyelesaikan karya tulis akhir ini.

7. Seluruh staf TU dan laboran, Mas Miftah dan Pak Joko yang bersedia

membantu setiap tahapan proses penelitian hingga penyelesaian tugas akhir

ini.

8. Sejawat FK UMM angkatan 2011 “Adorables” atas dukungan, bantuan, dan

kerjasamanya. Semoga kelak dapat menjadi dokter-dokter profesional yang

dapat bermanfaat bagi orang lain serta dapat menjalankan amanah sebagai

dokter karena Allah SWT.

9. Sahabat-sahabat terbaik yang selalu membantu selama penyelesaian karya

tulis akhir ini, Mariyah,Lilly, Tari, Alfi, Laksita, Putrinda, Kinanthi, Jeanny,

Ilma, Dwi, Friska, Hakimah, terimakasih atas doa, dukungan dan bantuan

yang telah diberikan selama ini.

10. Kelompok Jintan Hitam Lilly, Muqsit, Rofwiun atas dukungan dan

kerjasama dalam penyelesaian karya tulis akhir ini.

11. Keluarga besar Skill laboratorium FK UMM atas doa dan dukungannya.

12. Keluarga Besar Al-Zahrawi FK UMM atas doa, dukungan serta bantuan

yang diberikan selama ini.

13. Semua pihak yang terlibat secara langsung maupun tidak langsung,

terimakasih atas bantuan dan dukungannya.

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Penulis menyadari bahwa tugas akhir ini masih jauh dari kesempurnaan.

Oleh karena itu, penulis sangat mengharapkan saran, kritik dan masukan yang

membangun. Dengan mengharapkan Keridhaan-Nya, semoga karya tulis ini dapat

menambah wawasan keilmuan dan bermanfaat bagi semua pihak.

Malang, Agustus 2015

Penulis

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DAFTAR ISI

Halaman

LEMBAR PENGESEHAN .....................................................................................i

LEMBAR PENGUJIAN .........................................................................................ii

KATA PENGANTAR ............................................................................................iii

ABSTRAK ..............................................................................................................vi

DAFTAR ISI ........................................................................................................viii

DAFTAR GAMBAR .............................................................................................xi

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

DAFTAR SINGKATAN ......................................................................................xiii

DAFTAR LAMPIRNAN ......................................................................................xiv

BAB 1 PENDAHULUAN

1.1 Latar Belakang .................................................................................................1

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

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

1.3.1 Tujuan Umum .........................................................................................4

1.3.2 Tujuan Khusus ........................................................................................4

1.4 Manfaat Penelitian ............................................................................................5

1.4.1 Akademis .................................................................................................5

1.4.2 Klinis .......................................................................................................5

BAB 2 TINJAUAN PUSTAKA

2.1 Kornea ...............................................................................................................6

2.1.1 Definisi ...................................................................................................6

2.1.2 Anatomi Kornea ......................................................................................7

2.2 Inflamasi .........................................................................................................10

2.2.1 Definisi ..................................................................................................10

2.2.2 Proses Inflamasi ....................................................................................11

2.3 Inflamasi Kornea ............................................................................................13

2.4 Jintan Hitam (Nigella sativa) ..........................................................................14

2.4.1 Definisi dan Taksonomi .........................................................................14

2.4.2 Komposisi Kimia Nigella sativa ...........................................................15

2.5 Thymoquinon ..................................................................................................17

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2.5.1 Definisi .................................................................................................17

2.5.2 Mekanisme Thymoquinon menghambat aktifasi

Nuclear Factor Kappa Beta (NF-Kβ) ...................................................18

2.6 Nuclear Factor Kappa Beta (NF-Kβ) ............................................................19

2.6.1 Definisi ..................................................................................................19

2.6.2 Struktur Nuclear Factor Kappa Beta (NF-Kβ) .....................................21

2.6.3 Mekanisme Nuclear Factor Kappa Beta (NF-Kβ) ...............................22

2.6.5 Aktivasi Nuclear Factor Kappa Beta (NF-Kβ) ....................................23

2.6.6 Jalur Aktivasi Nuclear Factor Kappa Beta (NF-Kβ) ............................24

BAB 3 KERANGKA KONSEP DAN HIPOTESIS

3.1 Kerangka Konsep ............................................................................................27

3.2 Hipotesis .........................................................................................................28

BAB 4 METODOLOGI PENELITIAN

4.1 Rancangan Penelitian .....................................................................................29

4.2 Tempat dan Waktu Penelitian ........................................................................29

4.3 Populasi dan Sampel .......................................................................................29

4.3.1 Populasi .................................................................................................29

4.3.2 Sampel ...................................................................................................29

4.3.3 Besar Sampel Penelitian .......................................................................30

4.3.4 Teknik Pengambilan Sampel ................................................................32

4.3.5 Karakteristik Sampel Penelitian ............................................................32

4.3.6 Variabel Penelitian ................................................................................33

4.3.7 Definisi Operasional Variabel Penelitian ..............................................33

4.4 Alat dan Bahan ...............................................................................................34

4.3.1 Alat .......................................................................................................34

4.3.2 Bahan ...................................................................................................34

4.5 Kerangka Operasional Penelitian ...................................................................35

4.6 Prosedur Penelitian ........................................................................................36

4.6.1 Adaptasi ................................................................................................36

4.6.2 Pembuatan Ekstrak Nigella sativa ........................................................36

4.6.3 Pembuatan Solusio Nigella sativa Tetes Mata Topikal .........................37

4.6.4 Perlakuan Sampel ..................................................................................37

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4.6.5 Pengambilan Sampel Kornea untuk Pengamatan

Ekspresi NF-Kβ .....................................................................................38

4.6.6 Pemeriksaan NF-Kβ dalam Metode Imunohistokimia .........................39

4.6.7 Pengamatan Ekpresi NF-Kβ dengan

Metode Imunhistokimia pada Kornea ...................................................40

4.6.8 Penghitungan Ekspresi NF-Kβ ..............................................................41

4.7 Analisa Data ...................................................................................................42

BAB 5 HASIL PENELITIAN DAN ANALISIS DATA

5.1 Hasil Penelitian ...............................................................................................37

5.2 Analisis Data ....................................................................................................38

5.2.1 Uji Kruskal Wallis ..................................................................................38

5.2.2 Uji Post-Hoc (Mann-Whitney) ...............................................................39

5.2.3 Uji Korelasi …………..........................................................................39

BAB 6 PEMBAHASAN ........................................................................................41

BAB 7 KESIMPULAN DAN SARAN

7.1 Kesimpulan ......................................................................................................52

7.2 Saran ................................................................................................................52

DAFTAR PUSTAKA ............................................................................................53

LAMPIRAN ...................... ...................................................................................59

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DAFTAR GAMBAR

Gambar Halaman

2.1 Anatomi Mata ...................................................................................................7

2.2 Anatomi Kornea ..............................................................................................9

2.3 Jintan Hitam (a) bunga dan (b) biji .................................................................14

2.4 Struktur Kimia Thymoquinon .........................................................................17

2.5 Mekanisme Thymoquinon Menghambat Aktifasi

Nuclear Factor Kappa Beta (NF-Kβ) ...........................................................18

2.6 Protein Nuclear Factor Kappa Beta (NF-Kβ) ................................................20

2.7 Kelas Nuclear Factor Kappa Beta (NF-Kβ) .................................................21

2.8 Mekanisme Nuclear Factor Kappa Beta (NF-Kβ) .........................................22

2.9 Jalur Aktifasi Nuclear Factor Kappa Beta (NF-Kβ) ......................................25

3.1 Kerangka Konsep ...........................................................................................26

4.1 Kerangka Operasional Penelitian ...................................................................34

4.2 Lokasi Pengambilan Sampel Kornea ..............................................................38

5.1 Gambaran ekspresi NF-Kβ ............................................................................44

5.2 Ekspresi NF-Kβ ..............................................................................................45

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DAFTAR TABEL

Tabel Halaman

2.1 Komposisi Kimia Nigella sativa .....................................................................16

2.2 Komposisi Minyak Nigella sativa ...................................................................16

4.1 Klasifikasi perhitungan NF-Kβ ........................................................................40

4.2 Jadwal Penelitian ............................................................................................41

5.1 Hasil Penelitian Ekspresi NF-Kβ pada Kornea

Mata Tikus (Rattus novergius strain wistar) Jantan .......................................44

5.2 Hasil Kruskal Wallis .......................................................................................46

5.3 Hasil Uji Post-Hoc (Mann-Whitney) ...............................................................46

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DAFTAR SINGKATAN

a-MSH : Alpha-Melanosit Stimulating Hormon

BAFF : B Cell Activating Factor

DBD : DNA-Binding Domain

DNA : Deoxyribonucleic Acid

DTQ : Dimmer Thymoquinone

IKK : IKB Kinase

NF-Kβ : Nuclear Factor Kappa Betta

NIK : NFkβ-Inducing Kinase

NLS : Localization Signals

NSO : Nigella sativa Oil

TGF : Transformidezzing beta Growth Factor

THQ : Thymohydroquinone

THY : Timol

TLR : Toll-Like Receptor

TNF : Tumor Necrosis Factor

TNFR : Tumor Necrosis Factor Receptor

TQ : Thymoquinone

RANK : Receptor Activator of Nuclear Factor Kb

RE : Response Elements

RHD : Rel Homology Domain

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DAFTAR LAMPIRAN

Halaman

Lampiran 1 : Data Hasil Penelitian ......................................................................59

Lampiran 2 : Analisis Data ..................................................................................60

Lampiran 3 : Dokumentasi Kegiatan ....................................................................66

Lampiran 4 : Surat Determinasi Tanaman ............................................................70

Lampiran 5 : Surat Keterangan Ekstrak Jintan Hitam .........................................71

Lampiran 6 : Surat Keterangan Laboratorium Biomedik .....................................72

Lampiran 7 : Surat Keterangan Kelaikan Etik ......................................................73

Lampiran 8 : Surat Keterangan Laboratorium Biomedik UB ...............................74

Lampiran 9 : Surat Keterangan Pembacaan PA ....................................................75

Lampiran 10 : Kartu Konsultasi Tugas Akhir .......................................................76

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DAFTAR PUSTAKA

Abdullah,et al, 2013, Expression of NF-kB and COX2 in Colorectal Cancer

among Native Indonesians: The Role of Inflammation in Colorectal

Carcinogenesis, ActaMedicaIndonesiana-The Indonesian Journal of

Internal Medicine, Halaman 187-192 (online)

http://www.inaactamedica.org/archives/2013/24045388.pdf diakses

25 Februari 2015.

Ahmad,et al, 2013, A review on therapeutic potential of Nigella sativa: A miracle

herb, Asian Pacific Journal of Tropical Biomedicine, Vol 3, No 5,

Halaman 337-352 (online) www.elsevier.com/locate/apjtb diakses 25

Februari 2015.

Baratawidjaya, Karnen G, Iris R, 2012, ImunologiDasaredisi 10,

FakultasKedokteranUniversitas Indonesia, Jakarta.

Biswell R., 2010, Kornea, In : Vaughan, Asbury, OftalmologiUmumEdisi 17,

EGC, Jakarta.

Clancy J, 2000, Basic Concepts in Immunology a Student's Survival Guide, the

McGraw-Hill companies, United states.

Crane et al, 2012, Mass Spectrometric Analyses of Phosphatidylcholines in Alkali-

Exposed Corneal Tissue, Investigative Ophthalmology & Visual

Science, Vol 53, No 11, Halaman 7122-7130 (online)

http://www.iovs.org/content/53/11/7122.full.pdf+html diakses 25

Februari 2015.

Dursumet al, 2012, Comparison of the effects of bevacizumab and ranibizumab

injection on corneal angiogenesis in an alkali burn induced model, Inj

J Ophthalmol, Vol , No 4, Halaman 448-451, (online)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3428539/pdf/ijo-05-

04-448.pdf diakses2 Februari 2015.

53

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Erdurmuset al, 2007, Inhibitory Effects of Topical Thymoquinone on Corneal

Neovascularization, Cornea, Vol 26, Halaman 715-719, (online)

http://www.researchgate.net diakses 28 Oktober 2014.

Eroschenko V P, 2012, Atlas HistologidiFiore, EGC, Jakarta.

Gagen D,.2011,Cellular and Molecular Mechanisms of Corneal Inflammation and

Wound Healing, Disertation Doctor of Philosophy, Houston College,

Houston.

Ibrahim, Zein S, et al, 2008, Protection by Nigella sativa against carbon

tetrachloride-induced downregulation of hepatic cytochrome P450

isozymes in rats, Japanese Journal of Veterinary Research, Vol 56, No

3, Halaman 119-128, (online)

http://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/35112/1/56-

3_p119-128.pdf diakses 28 Oktober 2014.

James, Bruce, et al, 2006, Leture notes: Oftalmologiedisikesembilan, Erlangga,

Jakarta.

Khan, et al, 2011, Anticancer Activities of Nigella Sativa (Black Cumin),Afr J

Tradit Complement Altern Med, Vol 8, Halaman 226-232, (online)

http://www.ajol.info/index.php/ajtcam/article/viewFile/67964/56060

diakses 24 Maret 2014.

Klausner, Eytan A, et al, 2007, Corneal gene therapy, Journal of Controlled

Release 124, Halaman 107–133, (online)

www.elsevier.com/locate/jconrel diakses 25 Februari 2015

Lin W W, Karin M, 2007. A Cytokine-Mediated Link Between Innate Immunity,

Inflamasi and Cancer, The Journal of Clinical Investigation, Vol 117,

No 5, Halaman 1175-1183 (online)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1857251/pdf/JCI0731

537.pdf diakses 25 Februari 2015.

54

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Morgan S R, 2014, Understanding the structural basis of corneal refractive

function and its modification via novel therapeutic approaches,

Thesis, Cardiff University, United Kingdom.

Notoarmodjo S, 2005, MetodologiPenelitianKesehatan, AsdiMahasatya, Jakarta.

O’Dea E, Alexande H, 2009, NF-kB Signaling, John Wiley & Sons Inc. Volume

1, Halaman 107-115, (online) www.wiley.com/wires/sysbio diakses

25 Desember 2014.

Paarakh P, 2010, Nigella sativa Linn – a Comprehensive Review, Indian Journal

of Natural Products and Resources, Vol 1, No 4, Halaman 409-429

(online)

http://probotanic.com/pdf_istrazivanja/crni_kumin/Sveobuhvatni%20

pregled%20zdravstvenih%20svojstava%20crnog%20kumina.pdf

diakses 24 Maret 2014.

Patil, et al, 2008, Heme Oxygenase-1 Induction Attenuates Corneal Inflammation

and Accelerates Wound Healing after Epithelial Injury. Investigative

Ophthalmology & Visual Science, Vol 49, No. 8, Halaman 3379-

3386, (online)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2574648/pdf/nihms61

129.pdf diakses 25 Februari 2015

Prajapati, et al, 2010, Role of NFkB in Various Immunological & Inflammatory

Disorders, International Journal of Toxicological and

Pharmacological Research, Vol 2, No 1, Halaman 35-39, (online)

www.ijtpr.com diakses 25 Desember 2014.

Rajsekhar, et al, 2011, Pharmacognosy and Pharmacology of Nigella Sativa-A

Review, International Research Journal of Pharmacy, Vol 2, No 11,

Hal 36-39, (online) www.irjponline.com diakses 25 Desember 2014.

Riordan-Eva, Paul, 2010, AnatomidanEmbriologi Mata, In: Riordan-Eva P, John

P, Whitcher, Vaughan & Asbury OftalmologiUmum, EGC. Jakarta.

55

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Salem M L, 2005, Immunomodulatory and therapeutic properties of the Nigella

sativa L. Seed, International Immunopharmacology, Vol 5. Halaman

1749–1770, (online) http://www.elsevier.com/locate/intimp

diakses 28 Oktober 2014.

Salim, et al, 2013, Thymoquinone Induces Mitochondria-Mediated Apoptosis in

Acute Lymphoblastic Leukaemia in Vitro, Molecules, Vol 18,

Halaman 11219-11240, (online) www.mdpi.com/journal/molecules

diakses 24 Maret 2014.

Salmani, et al, 2014, Aqueous Solubility and Degradation Kinetics of the

Phytochemical Anticancer Thymoquinone; Probing the Effects of

Solvents, pH and Light, Molecules, Vol 19, Halaman 5925-5939,

(online) www.mdpi.com/journal/molecules diakses 24 Maret 2014.

Sandhu KS, AC Rana, 2013, A Review of Plant Nigella Sativa: A Brief

Consideration of Its PharmacognosticCharacteers, Chemical

Constitutents and Therapeutic Benefits, Pharma Science Monitor An

International Journal Of Pharmaceutical Sciences, Vol 4, Issue 4, Hal

323-343, (online) www.pharmasm.com diakses 25 Desember 2014.

Sangi S, et al, 2014, Hepatoprotective Effects of Oleuropein. Thymoquinone and

Fruit of Phoenix Dactylifera on Ccl4, Induced Hepatotoxicity In Rats,

World Journal of Pharmaceutical ReseaRch, Volume 3, Issue 2,

Halaman 3475-3486, (online) www.wjpr.net diakses 25 Desember

2014.

Saryono, 2011,

MetodologiPenelitianKesehatanPenuntunPraktisBagiPemula.MitraCe

ndika Press, Yogyakarta.

Sethi G, et al, 2008, Targeting Nuclear Factor-KB Activation Pathway by

Thymoquinone: Role in Suppression of Antiapoptotic Gene Products

and Enhancement of Apoptosis, Mol Cancer Res, Vol 6, Halaman

1059-1070, (online)

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http://mcr.aacrjournals.org/content/6/6/1059.full.pdf diakses 25

Februari 2015.

Siomek A, 2012, NF-κB Signaling Pathway and Free Radical Impact,

ActaBiochimicaPolonica, Vol 59, No 3, Halaman 323–331, (online)

www.actabp.pl diakses 25 Desember 2014.

Smolin, Throft’s, 2005, The Cornea Scientific Foundations and Clinical Practice

Fourth Edition,Lippincontt Williams & Wilkin, USA.

Sofia O, Rosy A, 2010, Effect of Genistein on Conjunctival Goblet Cells Density

and the Expression of Interleukin-1b in Ovariectomized Rats,

JurnalOftalmologi Indonesia, Vol 7, No. 3, Halaman 110-115,

(online)

http://journal.unair.ac.id/filerPDF/JOI%20Vol%207%20No%203%20

Juni%202010%20%28Ovi%20S%29.pdf diakses 28 Oktober 2014.

Stautd L, Micheal Karin, 2009, The Nuclear Factor NF-Kβ Pathway in

Inflammation, Cold Spring Harbor Laboratory Press, France.

Supranto J, 2007, StatistikTeoridanAplikasiEdisi 6, Erlangga, Jakarta.

Sutphin, et al, 2008.Basic and Clinical Science Course External Disease and

Cornea Section 8,American Academy of Opthalmologi, USA.

Tembhurne S V, et al, 2014, A Review on Therapeutic Potential of Nigella Sativa

(Kalonji) Seeds, Journal Of Medicinal Plants Research, Vol 8, No 3,

Hal 167-177, (online) http://www.academicjournals.org/JMPR

diakses 25 Desember 2014.

Toropainen E, 2007, Corneal Epithelial Cell Culture Model for Pharmaceutical

Studies, Doctoral Dissertation, University of Kuopio, Finland.

Yenita, 2010, PengaruhPemberianEkstrakJaheterhadap Kadar Malondialdehide

(MDA) Testis dan Diameter TubulusSeminiferusTestis Mencit yang

diberiPlumbumAsetat, JurnalKedokteranIbnuSina, Vol 5, No 3,

Halaman 106.

57

Page 19: PENGARUH EKSTRAK JINTAN HITAM ( ) TOPIKAL TETES MATA ... · PDF filehasil penelitian pengaruh ekstrak jintan hitam (nigella sativa) topikal tetes mata terhadap penurunan ekspresi nuclear

Wei Gu, et al, 2011, Effects of Amniotic Membrane Transplantation on Cytokines

Expression in Chemically Burned Rat Corneas, Int J Ophtthalmol,

Vol 4, No 1, Halaman 33-36, (online)

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3340686/pdf/ijo-04-

01-033.pdf diakses 25 Februari 2015.

Xiao, Gutian, Jing F, 2011, Nf-Kb and Cancer: A Paradigm Of Yin-Yang, Am J

Cancer Res, Vol 1, No 2, Halaman 192-221, (online) www.ajcr.us

diakses 25 Desember 2014.

Zhang,et al, 2005, Plasminogen Kringle 5 Inhibits Alkali-Burn–Induced Corneal

Neovascularization, Investigative Ophthalmology & Visual Science,

Vol 46, No 11, Halaman 4062-4071 (online)

http://www.ncbi.nlm.nih.gov/pubmed/16249481 diakses 25 Februari

2015.

58