Post on 07-Jun-2019
KARYA TULIS AKHIR
PENGARUH PEMBERIAN EKSTRAK BIJI JINTEN HITAM
(Nigella Sativa) TERHADAP PERBAIKAN TUBULUS PROKSIMAL
PADA TIKUS MODEL KERUSAKAN GINJAL KRONIK
Oleh:
FIFA YUNIARMI
201310330311054
FAKULTAS KEDOKTERAN
UNIVERSITAS MUHAMMADIYAH MALANG
2017
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HASIL PENELITIAN
PENGARUH PEMBERIAN EKSTRAK BIJI JINTEN HITAM
(Nigella Sativa) TERHADAP PERBAIKAN TUBULUS PROKSIMAL
PADA TIKUS MODEL KERUSAKAN GINJAL KRONIK
KARYA TULIS AKHIR
Diajukan kepada
Universitas Muhammadiyah Malang
Untuk Memenuhi Salah Satu Persyaratan
Dalam Menyelesaikan Program Sarjana
Fakultas Kedokteran
Oleh :
FIFA YUNIARMI
201310330311054
FAKULTAS KEDOKTERAN
UNIVERSITAS MUHAMMADIYAH MALANG
2017
iii
iv
v
KATA PENGANTAR
Assalamu’alaikum wr.wb
Puji syukur penulis panjatkan kehadirat Allah SWT karena atas
rahmat dan hidayah-Nya, penulisan proposal tugas akhir ini dapat diselesaikan
dengan baik. Sholawat serta salam selalu tercurahkan kepada Rasulullah SAW,
keluarga, para sahabat dan pengikut beliau hingga akhir zaman.
Penelitian dalam proposal tugas akhir ini berjudul “Pengaruh Ekstrak Biji
Jinten Hitam (Nigella sativa) Terhadap Perbaikan Tubulus Proksimal Tikus
Model Kerusakan Ginjal Kronik ”. Tugas akhir ini diajukan untuk memenuhi
persyaratan Pendidikan Sarjana Fakultas Kedokteran Universitas Muhammadiyah
Malang.
Penulis menyadari bahwa penulisan ini masih jauh dari sempurna, 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, 19 Januari 2017
Penulis
vi
DAFTAR ISI
HALAMAN JUDUL .......................................................................................... ..i
LEMBAR PENGESAHAN ...............................................................................iii
LEMBAR PENGUJIAN ....................................................................................vi
KATA PENGANTAR ........................................................................................ v
UCAPAN TERIMAKASIH .............................................................................vii
ABSTRAK ......................................................................................................viii
ABSTRAK ..........................................................................................................ix
DAFTAR ISI ...................................................................................................... x
DAFTAR TABEL ........................................................................................... xiv
DAFTAR GAMBAR ....................................................................................... xv
DAFTAR SINGKATAN ................................................................................ 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 ..................................................................................... 3
1.4 Manfaat Penelitian ...................................................................................... 4
1.4.1 Manfaat akademik ............................................................................. 4
1.4.2 Manfaat klinis .................................................................................... 4
1.4.3 Manfaat masyarakat ........................................................................... 4
BAB 2 : TINJAUAN PUSTAKA ...................................................................... 5
vii
2.1 Jejas sel ....................................................................................................... 5
2.1.1 Jejas sel reversibel ............................................................................... 6
2.1.2 Jejas sel irreversibel ........................................................................... 7
2.1.3 Inflamasi ........................................................................................... 10
2.1.3.1 Perjalanan inflamasi ............................................................. 13
2.1.3.2 Inflamasi akut ....................................................................... 13
2.1.3.3 Inflamasi kronis .................................................................... 14
2.2 Ginjal .......................................................................................................... 16
2.2.1 Anatomi dan histologi ........................................................................ 16
2.2.2 Fisiologi ............................................................................................. 23
2.3 Kerusakan ginjal ........................................................................................ 25
2.3.1 Gagal ginjal kronis ............................................................................ 26
2.3.2 Penyebab jejas pada ginjal akibat carbon tetrachloride .................... 32
2.3.3 Mekanisme perbaikan jejas pada ginjal pasca injuri ......................... 33
2.4 Jinten hitam ................................................................................................. 35
2.4.1 Toksonomi dan morfologi jinten hitam ............................................. 35
2.4.2 Kandungan biji jinten hitam ............................................................. 37
2.4.3 Kegunaan biji jinten hitam .............................................................. 39
2.4.3.1 antiinflamasi pada jinten hitam .......................................... 41
2.4.4 Peran jinten hitam dalam perbaikan ginjal pasca injury ................... 42
2.5 Tikus Putih (Rattus norvegicus).....................................................................42
BAB 3 : KERANGKA KONSEP DAN HIPOTESIS PENELITIAN ............... 46
3.1 Kerangka Konseptual Penelitian .................................................................. 46
3.2 Hipotesis Penelitian ...................................................................................... 49
viii
BAB 4 : METODE PENELITIAN .................................................................... 50
4.1 Rancangan Penelitian ................................................................................... 50
4.2 Tempat dan Waktu Penelitian ....................................................................... 50
4.3 Populasi dan Sampel ..................................................................................... 50
4.3.1 Populasi .............................................................................................. 50
4.3.2 Sampel ................................................................................................ 50
4.3.3 Hitung replikasi .................................................................................. 50
4.3.4 Teknik sampel .................................................................................... 52
4.3.5 Karakteristik Sampel Penelitian ......................................................... 52
4.4 Variabel Penelitian ....................................................................................... 52
4.4.1 Variabel bebas .................................................................................... 52
4.4.2 Variabel tergantung ............................................................................ 53
4.5 Definisi Operasional ..................................................................................... 53
4.6 Alat dan Bahan Penelitian ............................................................................ 54
4.6.1 Alat ...................................................................................................... 54
4.6.2 Bahan .................................................................................................. 55
4.7 Prosedur Penelitian ....................................................................................... 56
4.7.1 Tahap persiapan .................................................................................. 56
4.7.2 Tahap pelaksanaan ............................................................................. 56
4.8 Alur penelitian .............................................................................................. 62
4.9 Analisis Data ................................................................................................ 63
4.10 Jadwal Penelitian..........................................................................................64
BAB 5 : HASIL PENELITIAN DAN ANALISIS DATA ..................................65
5.1 Hasil Penelitian ..............................................................................................65
5.2 Analisis Data..................................................................................................68
ix
BAB 6 : PEMBAHASAN ...................................................................................71
BAB 7 : KESIMPULAN DAN SARAN ............................................................75
DAFTAR PUSTAKA ........................................................................................ 77
LAMPIRAN.........................................................................................................81
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DAFTAR TABEL
Tabel Halaman
1.1 Jadwal Penelitian ............................................................................................ 58
5.1 Jumlah rerata hialin cast tubulus proksimal ginjal tikus putih....................... 67
5.2 Uji analisis Statistik Tukey............................................................................. 68
xi
DAFTAR GAMBAR
Gambar Halaman
2.1 Jejas pada Sel.................................................................................................. 10
2.2 Komponen Respon Radang............................................................................. 11
2.3 Penyebab dan Dampak Inflamasi Kronis ....................................................... 15
2.4 Mediator Inflamasi.......................................................................................... 16
2.5 Anatomi Ginjal................................................................................................ 17
2.6 Nefron Manusia............................................................................................... 22
2.7 Hialin cast........................................................................................................29
2.8 Jintem Hitam....................................................................................................36
2.9 Flavonoid ........................................................................................................38
2.10 Adrenal dan Ginjal pada Tikus......................................................................45
5.1 Gambaran Hialin cast .................................................................................... 66
5.2 Grafik Hasil Uji Linier ...................................................................................69
xii
DAFTAR SINGKATAN
AGEs : Advanced Glicosylation End Products
CCL3 : Radical trichlormetil
CCL4 : Carbon tetrachloride
IL-1β : Interleukin- 1 beta
IFN-γ : Interferon gamma
TNF-α : Tumor necrosis factor alpha
ATP : Adenosia trifosfat
ICAM-1 : Intercellular adhesion molecule 1
CYP2E1 : Cytochrome P450 2E1
OOCCl3 : Radical triklorometil perokside
LOOH : Lipid hidroperoksidase
LO : Radical lipid alkoksil
GST : Glutation-S-transferase
GSH : Reduced glutatione
EGF : Epidermal growth factor
PAI-1 : Plasminogen activators inhibitor 1
SOD : Superoxide dismutase
COX-2 : Cyclooxigenase 2
PGE2 : Prostaglandin E2
MSG : Monosodium glutamat
xiii
Daftar Pustaka
Aina abata, Qorry. 2014. Ilmu Penyakit Dalam. Yaasan PP Al-Furqon. Madiun
Anirudhan, A. 2015. Saponins Isolated from Roots of Chlorophytum borivilanum
reduce acute and chronic inflamation and histone deacetylase. India. pp.
27-37.
Anonim, 2009, Majalah Naturakos, Vol IV/NO 12, Badan POM RI, Jakarta.
Aravinthan, adithann. 2014. Ginseng total saponin attenuates myocardial injury
via anti- oxidative and anti-inflammatory properties. Avaiable at
http://www.ginsengres.org. Accesed november 2015
Badan Pengawas Obat dan Makanan (POM) Republik Indonesia. 2009. Mengenal
Manfaat Jintan Hitam sebagai Obat Bahan Alam. Naturakos 4(12) p: 2-6
Baratawidjaja Garna, Karnen. Iris rengganis. 2010. Imunologi Dasar. Fakultas
Kedokteran Universitas Indonesia. Jakarta
Blue Histology – urinary system. 2009. School of Anatomy and Human Biology –
University of Western Australia.
http://www.lab.anhb.uwa.edu.au/mb140/corepages/urinary/urinary.htm.
Australia.
Da Silva. Milena. 2013. Anti-inflammatory effects of Carvacrol: Evidence for a
Key Role of Interleukin-10. www.elsevier.com/locate/ejphar European
Journal of Pharmacology. 2013
Faroon Obaid. Jessilyn Taylor, et al. 2005. Toxicological Profile for Carbon
Tetrachloride. US Departement of Healthy and Human Services. Atlanta,
Georgia.
Gartner, Leshlie P. 2007. Color Atlas and Text of Histology 6th Edition. Wolters
Kluwer Health
Hurairah, Um. 2014. Black Seed (Nigella Sativa) the miraculous healing power
for all deseases. Jordan
Husaeni, Rijal Kamaluddin. 2008. Efek Ekstrak Air Buah Tin Terhadap Kadar
Glukosa Darah Tikus Putih Jantan Galur Wistar (Rattus norvegicus L)
yang di Induksi Aloksan Monohidrat, Tesis, Institut Teknologi Bandung,
Bandung. 67 - 68.
Hutapea, Johnny Ria. 1994. Inventaris Tanaman Obat Indonesia. Jakarta: Depkes
RI. pp: 163-4
Hwang, YP, Choi, JH, Yun, HJ, el al, 2011, Anthocyanins from purple sweet
potato attenuate dimethylnitrosamine-induced liver injury in rats by
xiv
reducing Nrf2-mediated antioxidant enzymes and reducing COX-2 and
iNOS expression, Food and Chemical Toxicology, vol. 49.
Ibraheem, N.K., Ahmed, J.H, & Hassan, M.K., 2010, The Effect of Fixed Oil and
Water Extracts of Nigella sativa on Sickle Cells: an in Vitro Study,
Singapore Med, 51(3) : 230-234
Katzung. Bertram G. Susan B. Masters. Anthony J. Trevor. 2002. Farmakologi
Dasar & Klinik. EGC. Jakarta
Keyhanmanash Rana. 2010. Effects of Thymoquinone on the Lung Pathology and
cytokine levels of Ovalbumins-sensitized guinea Pigs. Institute of
Pharmacology Polish Academi of Sciences. 2010
Lakhanpal. Parul and Deepak Kumar Rai. 2007. A Versatile Flavonoid. Internet
Journal of Medical Update, Vol. 2. Mauritius
Laura, L. 2014. Histopathology of Chronic Kidney Disease of Unknown Etiology
in Salvadoran Agricultural Communities. MEDICC review vol 16 No 2
2014
Lee Gippeum et al. 2005. Diagnostic Evaluation of Carbon Tetrachloride-
indused Rat Hepatic Cirrhosis Model. Department of Veterinary
Pathology. Korea . 25: 1029-1038
Leong Xin-Fang, Mohd Rais Mustafa, and Kamsiah Jaarin. 2013. Nigella sativa
and Its Protective Role in Oxidative Stress and Hypertension. Hindawi
Publishing Corporation. Malaysia. pp 896-906.
Li, Y.2015. Attenuation of Inflammation by Emodin in Lipopolysaccharide
induced Acute Kidney Injury viaInhibition of Toll-like Receptor 2 Signal
Pathway. Departement of neprology, chongqing hospitalof tradional
chininese medicine, chongqing. China
Lindner, LE. Haber, MH. 1983. Hyaline Cast in the Urine: Mechanism of
Formation and Morphologic Transformations. Department of Pathology
and Laboratory Medicine, Texas. USA
Li Zhang-Qiu. 2008. Prevalence of Chronic Kidney Disease in Population-based
studies: Systematic Review. BioMed Central. Heidelberg, Germany.
Malhotra, S. K. 2012. Handbook of Herb, Nigella Ed.2 Vol.2, Woodhead
Publishing Limited. India
Manggarwati Andinafitriana. 2010. Uji Toksikologi Subkronis Ekstrak Valerian
Pada Tikus Wistar. Fakultas Kedokteran Undip, Semarang
Meschers L, Anthony. 2005. Histologi Dasar Junqueira. EGC. Jakarta
xv
Noor, N.A., & Mourad, M., 2010, Evaluation of Antioxidant Effect of Nigella
sativa Oil on Monosodium Glutamate induced Oxidative Stress in Rat
Brain, J. Am. Sci., 6(12) : 13-18
Parandin rohmatollah. 2012. The Enhancing Effects of Alcoholic Extract of
Nigella Sativa Seed on Fertility Potential, Plasma gonadotropins and
Testosterone in Male Rats. Iran 2012
Paul. Kimbel L, Mark E. Rosenberg. 2015. Chronic Renal Disease.
www.elsevier.com . USA
Treuting Piper M. Suzanne M. Dintzis. 2012. Comparative Anatomy and
Histology a Mouse and Human Atlas. Academic Press. Amerika. 29-30
Robbins. Kumar. Cotran. 2010. Buku Ajar Patology. EGC. Jakarta
Price, A Sylvia. Wilson. 2006. Patofisiologi: konsep-konsep klinis Proses
penyakit Edisi IV. EGC. Jakarta
Rahayu Wulan Puji. 2012. Aktifitas Antiproliveratif Jinten Hitam (Nigella sativa)
Pada sel paeru tikus yang diinduksi DMBA. Makara Kesehatan. 2012 : 51-
56
Ramadan, MF. & Mörsel, JT. 2001. Neutral Lipid Classes Of Black Cumin
(Nigella Sativa L.) Seed Oil. Technische University Berlin. Germany
Riset Kesehatan Dasar. Badan Penelitian dan Pengembangan Kesehatan
Kementrian Kesehatan RI Tahun 2013. Jakarta
Sahreen Sumaira, et al. 2015. Protektive effects opaca fruits against CCl4-
Induced Oxidative Kidney Lipid Peroxidation And Trauma In Rat.
Botanical SciencesDivision. Pakistan 59: 28438.
Santres E. Zacharias. 2015. The Bioactivity and Toxicological Actions of
Carvacrol. Department of Biology. Canada 55: 304-318.
Saricicek edibe, et al. 2014. Effect of Nigella sativa on experimental liver fibrosis.
Biomedical Research. India 25 (1): 32-38.
Sharma, Neraaj Kumar. 2011. Pharmacognostic Standardization, Physico and
Phytocemical Evaluation Of Nigella Sativa Linn. Seed. International
Journal of Pharmaceutical Sciences Research. India
Soepraptini Julien, Safda Farizy Ridho, Koesnoto SP. 2012. Gambaran
Histopatologi Ginjal Tikus Putih Jantan Pada Kasus Patah Tulang Femur
Dengan Terapi Ekstrak Tanaman Cissus quadrangularis dan Kalsium
Karbonat. Departemen Klinik Veteriner. FKH UNAIR. Surabaya
xvi
Susianti. 2013. Pengaruh Ekstrak Biji Jinten Hitam (Nigella Sativa) Terhadap
Gambaran Histopatologi Hepar, Paru, dan Testis Tikus Putih (Rattus
Norvegicus) yang Diinduksi Gentamisin. Bagian Histopatologi Fakultas
Kedokteran Lampung. Lampung. 107-118
Tucker S. Patrick. 2015. Chronic Kidney Disease Influences Multiple System:
Describing the Relationship between Oxidative Stress, Inflamation,
Kidney Damage, and Concomitant Disease. Australia
United States Renal Data System. 2009. Annual report States Renal Data System.
Avaiable at http://www.USRDS.ORG. Accesedoktober 2015.
Ueroschenco. Victor P. 2012. Atlas Histologi diFiore. EGC. Jakarta
Venkatanarayana G, Sudhakara G. 2012. Protective Effects of Curcumin and
Vitamin E on Carbon Tetrachloride-Induced Nephrotoxicity in Rats.
EXCLJ Journal 2012;11:641-650 – ISSN 1611-2156. India
World Healt Organization. 1999. Carbon Tetrachloride. Geneva. 2004
Yang Yanyan , Jongsung Lee , Man Hee Rhee et al. 2014 Molecular mechanism
of protopanaxadiol saponin fraction-mediated anti-inflammatory actions.
Elsevier . Korea
Yusuf, Mentari Syahirah. 2014. Efektivitas Penggunaan Jintan Hitam (Nigella
Sativa) dalam Proses Percepatan Penyembuhan Luka Setelah Pencabutan
Gigi, Universitas Hasanuddin, Fakultas Kedokteran Gigi, Bagian Ilmu
Bedah Mulut, Skripsi (Dipublikasikan). Fakultas Kedokteran Gigi
Universitas Hasanuddin. Makassar