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Oleh: LILLY NURFITRIA RAMADHANI 201110330311075 · PDF filedr. Dian Yuliartha, Sp.PA, atas...
Transcript of Oleh: LILLY NURFITRIA RAMADHANI 201110330311075 · PDF filedr. Dian Yuliartha, Sp.PA, atas...
KARYA TULIS AKHIR
PERBEDAAN POTENSI EKSTRAK JINTAN HITAM (Nigella sativa)
TOPIKAL BERBAGAI DOSIS DENGAN NATRIUM DIKLOFENAK
TOPIKAL DALAM MENURUNKAN EKSPRESI TUMOR NECROSIS
FACTOR α (TNFα) PADA KORNEA TIKUS PUTIH JANTAN (Rattus
novergicus strain wistar) MODEL INFLAMASI
Oleh:
LILLY NURFITRIA RAMADHANI
201110330311075
UNIVERSITAS MUHAMMADIYAH MALANG
FAKULTAS KEDOKTERAN
2015
HASIL PENELITIAN
PERBEDAAN POTENSI EKSTRAK JINTAN HITAM (Nigella sativa) TOPIKAL
BERBAGAI DOSIS DENGAN NATRIUM DIKLOFENAK TOPIKAL DALAM
MENURUNKAN EKSPRESI TUMOR NECROSIS FACTOR α (TNFα) PADA
KORNEA TIKUS PUTIH JANTAN (Rattus novergicus strain wistar)
MODEL INFLAMASI
KARYA TULIS AKHIR
Diajukan kepada
Universitas Muhammadiyah Malang
Untuk Memenuhi Salah Satu Persyaratan
Dalam Menyelesaikan Program Sarjana
Fakultas Kedokteran
Oleh :
LILLY NURFITRIA RAMADHANI
201110330311075
UNIVERSITAS MUHAMMADIYAH MALANG
FAKULTAS KEDOKTERAN
2015
iii
KATA PENGANTAR
Puji syukur kehadirat Allah SWT Yang Maha Pengasih lagi Maha
Penyayang, Yang Maha Pemberi semua nikmat, kebaikan, dan kekuatan selama
proses pelaksanaan, Yang Maha Menyimpan rahasia hikmah di balik semua
peristiwa, Yang Maha Memudahkan, 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 “ Perbandingan Pemberian Ekstrak
Jintan Hitam (Nigella sativa) Topikal dengan Natrium Diklofenak Topikal
Terhadap Penurunan Ekspresi Tumor Necrosis Factor α (TNFα) Pada Kornea
Tikus Putih Jantan (Rattus novergicus strain wistar) Model Inflamasi”. Tugas
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, selaku Dekan Fakultas Kedokteran Universitas
Muhammadiyah Malang atas ilmu dan bimbingannya selama di Fakultas
Kedokteran UMM.
2. dr. Moch. Ma’roef, Sp.OG, selaku Pembantu Dekan I Fakultas Kedokteran
UMM atas kesediaan waktu dan penyampaian ilmu yang sangat bermanfaat
bagi masa depan para mahasiswa FK UMM.
3. dr. Rahayu, Sp.S, selaku Pembantu dekan II Fakultas Kedokteran UMM
yang senantiasa bersabar dalam membimbing dan mengajarkan ilmunya
kepada kami.
iv
4. dr. Iwan Sys Indrawanto, Sp.KJ selaku Pembantu Dekan III, yang penuh
semangat dalam menyampaikan ilmu dan motivasi yang membangun
semangat kami selama menjalani pendidikan di Fakultas Kedokteran.
5. dr. Alfa Sylvestris Sp.M, selaku pembimbing 1, atas kesabaran, kebaikan
hati, serta kesediaan dalam meluangkan waktu dalam membimbing hingga
dapat menyelesaikan penelitian ini dengan baik.
6. dr. Diah Hermayanti Sp.PK, selaku pembimbing 2, atas kesabaran, kebaikan
hati, serta kesediaan dalam meluangkan waktu dalam membimbing penulis
hingga dapat menyelesaikan penelitian ini dengan baik.
7. dr. Isbandiyah Sp.PD, selaku penguji tugas akhir ini, atas segala masukan
dan arahan yang sangat bermanfaat dalam pengerjaan tugas akhir ini dan
kesediaan waktu, sehingga tugas ini dapat diselesaikan dengan baik.
8. dr. Dian Yuliartha, Sp.PA, atas kebaikan dan kesediaan meluangkan waktu
untuk membantu dalam proses pengamatan hasil penelitian.
9. Ibu, bapak, atas doa dan lelah yang diberikan dari pagi hingga pagi lagi,
serta dukungan moril dan materil yang tak pernah putus agar tugas ini dapat
selesai dengan baik. Mas Adi dan Bagus, terimakasih sudah menjadi kakak
dan adik terbaik yang membuat penulis selalu ingin kembali ke rumah.
10. Seluruh staf TU dan laboran, Mas Miftah dan Pak Joko yang bersedia
membantu setiap tahapan proses penelitian hingga penyelesaian tugas akhir
ini.
11. Pak wibi, ibu fitri dan seluruh staf Laboratorium Biokima UB, yang
bersedia membantu setiap tahapan proses penelitian hingga penyelesaian
tugas akhir ini.
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12. Kawan seperjuangan “Grup Jintan Hitam” Imaniyah, Muqsit, Rofwiun
13. Sahabat-sahabat terbaik yang menjadi keluarga selama di Malang,
Imaniyah, Dwi, Friska, Hakimah, Laksita, Jeanny, Kinanthi, Putrinda,
Mariyah, Tari, Alfi, Mba Dwi, Linda, Dea terimakasih atas kebersamaan
yang sederhana, bantuan, kesabaran, motivasi, dukungan, dan semua yang
telah diberikan.
14. Sejawat FK UMM angkatan 2011, Adorables, atas dukungan, bantuan, dan
kerjasamanya. Semoga kelak dapat menjadi dokter-dokter profesional yang
barokah, sukses dunia akhirat, dan senantiasa dalam ketaatan kepada Allah
SWT.
15. Semua pihak yang terlibat secara langsung maupun tidak langsung,
terimakasih atas bantuan dan dukungannya.
Penulis menyadari bahwa tugas akhir ini masih jauh dari kata
sempurna. Oleh karena itu, penulis sangat mengharapkan saran dan
masukan yang membangun. Dengan mengharapkan Keridhaan-Nya, semoga
karya tulis ini dapat menambah wawasan keilmuan dan bermanfaat bagi
semua pihak.
Malang, 27 Agustus 2015
Penulis
viii
DAFTAR ISI
LEMBAR PENGESAHAN .................................................................................. i LEMBAR PENGUJIAN ...................................................................................... ii
KATA PENGANTAR ........................................................................................ iii ABSTRAK .......................................................... Error! Bookmark not defined.
ABSTRACT ........................................................ Error! Bookmark not defined. DAFTAR ISI .................................................................................................... viii
DAFTAR TABEL ............................................................................................... x DAFTAR GAMBAR .......................................................................................... xi
DAFTAR LAMPIRAN ...................................................................................... xii DAFTAR SINGKATAN .................................................................................. xiii
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 Akademis ................................................................... 4
1.4.2 Manfaat Klinis ......................................................................... 4
BAB 2 TINJAUAN PUSTAKA ........................................................................... 5
2.1 Jintan Hitam (Nigella sativa)............................................................. 5
2.1.1 Taksonomi dan Deskripsi Jintan Hitam (Nigella sativa) ........... 5
2.1.2 Kandungan Biji Jintan Hitam (Nigella sativa) .......................... 6
2.1.3 Ekstrak Jintan Hitam (Nigella sativa) Sebagai Anti-inflamasi ... 7
2.1.4 Fixed oil pada Jintan Hitam (Nigella sativa) ............................. 8
2.1.5 Thymoquinone pada Jintan Hitam (Nigella sativa) .................... 9
2.2 Kornea ............................................................................................ 10
2.2.1 Histologi dan Fisiologi Kornea ............................................... 10
2.2.2 Imunologi Kornea .................................................................. 12
2.3 Inflamasi Kornea............................................................................. 14
2.3.1 Inflamasi Kornea Akibat Trauma Alkali (NaOH) ................... 16
2.3.2 Peran TNFα pada Inflamasi Steril Kornea .............................. 19
2.4 Non-steroidal Anti-inflammatory Drug (NSAID) ............................ 21
BAB 3 KERANGKA KONSEPTUAL DAN HIPOTESIS ................................. 23 3.1 Kerangka Konseptual ...................................................................... 23
3.2 Hipotesis ......................................................................................... 25
BAB 4 METODOLOGI PENILITIAN .............................................................. 26 4.1 Rancangan Penelitian ...................................................................... 26
ix
4.2 Tempat dan Waktu Penelitian ......................................................... 26
4.3 Populasi dan Sampel ....................................................................... 26
4.3.1 Populasi ................................................................................. 26
4.3.4 Teknik Pengambilan Sampel .................................................. 28
4.3.5 Karakteristik Sampel Penelitian .............................................. 28
4.3.6 Variabel Penelitian ................................................................. 28
4.3.7 Definisi Oprasional Variabel Penelitian .................................. 28
4.4 Alat dan Bahan Penelitian ............................................................... 29
4.4.1 Alat ........................................................................................ 29
4.4.2 Bahan ..................................................................................... 30
4.5 Prosedur Penelitian ......................................................................... 31
4.5.1 Pembuatan Ekstrak Jintan Hitam (Nigella sativa) Topikal
Tetes Mata.............................................................................. 31
4.5.2 Sediaan Natrium Diklofenak 1% tetes mata topikal ................ 32
4.5.3 Perlakuan Sampel ................................................................... 32
4.5.4 Adaptasi ................................................................................. 33
4.5.5 Pengambilan Sampel Kornea .................................................. 33
4.5.7 Penghitungan Ekspresi TNFα ................................................. 37
4.6 Analisis Statistik ............................................................................. 37
4.7 Alur Penelitian ................................................................................ 38
4.8 Penguburan Tikus Percobaan .......................................................... 39
BAB 5 HASIL PENELITIAN DAN ANALISIS DATA .................................... 40
5.1 Hasil Penelitian ............................................................................... 40
5.2 Analisis Data .................................................................................. 41
5.2.1 Uji Normalitas ........................................................................ 41
5.2.2 Uji Statistik Non-Parametric Kruskal-Wallis .......................... 41
5.2.3 Uji Post Hoc Mann-Whitney .................................................. 42
BAB 6 PEMBAHASAN .................................................................................... 44
BAB 7 KESIMPULAN DAN SARAN .............................................................. 48 7.1 Kesimpulan ..................................................................................... 48
7.2 Saran............................................................................................... 48
DAFTAR PUSTAKA ........................................................................................ 49 LAMPIRAN ...................................................................................................... 55
x
DAFTAR TABEL
Tabel Halaman
2.1 Bahan Aktif Nigella sativa ………...…………………………….………. 7
2.2 Klasifikasi trauma alkali .............................................................................. 18
2.3 Fase penyembuhan pada defek kornea akibat trauma alkali ....................... 19
4.1 Scoring TNF α untuk Analisis Semikuantitatif............................................. 29
5.1 Hasil Pengamatan Ekspresi TNFα pada kornea tikus putih jantan
(Rattus novergicus strain wistar) Model Inflamasi..................................... 40
5.2 Hasil Uji Normalitas (Shapiro-Wilk)............................................................ 41
5.3 Hasil Uji Kruskal-Wallis............................................................................... 42
5.4 Perbandingan Nilai Asymp. Sig. dari Uji Mann-Whitney
Semua Kelompok Uji ................................................................................... 42
xi
DAFTAR GAMBAR
Gambar Halaman
2.1 Tanaman, bunga dan biji (Nigella sativa) .................................................... 5
2.2 Usulan jalur biosintesis thymoquinone dalam biji (Nigella sativa) .............. 9
2.3 Potongan melintang kornea .......................................................................... 11
2.4. Konsep mekanis migrasi neutrofil ke daerah cedera kornea ...................... 13
2.5 Mekanisme inflamasi steril ........................................................................... 18
4.1 Lokasi pengambilan sampel kornea .............................................................. 33
4.2 Gambaran TNFα dalam pewarnaan imunohistokimia ................................. 37
5.1 Grafik Hasil Pengamatan Ekspresi TNFα pada Kornea Tikus Putih
Jantan (Rattusnovergicus strain wistar) ...................................................... 40
xii
DAFTAR LAMPIRAN
Lampiran Halaman
Lampiran 1 Data Primer Hasil Penelitian .......................................................… 55
Lampiran 2 Analisis Data Statistik .................................................................… 56
Lampiran 3 Dokumentasi Penelitian ................................................................... 63
Lampiran 4 Determinasi Tanaman Jintan hitam ................................................. 65
Lampiran 5 Surat Keterangan Ekstrak Jintan Hitam ......................................... 66
Lampiran 6 Surat Keterangan Penelitian Lab. Biokimia UB ............................. 67
Lampiran 7 Surat Keterangan Penelitian Lab. Biomedik UMM ....................... 68
Lampiran 8 Surat Keterangan Kelaikan Etik ...................................................... 69
Lampiran 9 Surat Keterangan Pembacaan PA .................................................... 70
Lampiran 10 Kartu Konsultasi Tugas Akhir ....................................................... 71
xiii
DAFTAR SINGKATAN
CME : cystoids macular edema
COX : cyclooxygenase
COX2 : cyclooxygenase 2
DAMPs : damage-associated molecular patterns
EGFR : epidermal growth factor receptor
GM-CSF : granulocyte-macrophage colony-stimulating factor
HMGB1 : high-mobility group box 1
IFNγ : Interferon γ
IL-1 : interleukin 1
IL1-R : IL-1 receptor
IL-1β : interleukin-1β
IL-6 : Interleukin 6
iNOS : inducible nitric oxide synthase
LC : langerhans cell
LT : leukotrien
MAPKs : mitogen-activated protein kinase
MMP 9 : matrix metalloproteinase 9
NK : natural killer
NLRP3 : nucleotide-binding oligomerization domain (NOD)-like receptor
and pyrin domain-containing 3
NO : nitric oxide
NOD : nucleotide-binding oligomerization domain
xiv
NSAID : nonsteroidal antiinflammatory drug
PBS : phosphate buffered saline
PEE : punctate epithelial erosion
PEK : punctate epithelial keratitis
PG : prostaglandin
PGD₂ : prostaglandin D₂
PGE₂ : prostaglandin E₂
PGF₂ : prostaglandin F₂
PGI₂ : prostaglandin I₂
PRR : pathogen recognition receptor
RAGE : receptor for advanced glycation end-product
ROI : reactive oxygen intermediates
TIO : tekananan intraokular
TLRs : toll-like receptor
TNFα : tumor necrosis factor α
TXA₂ : tromboxsan A₂
WHO : world health organization
49
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