Korelasi Antara Ekspresi Endothelial Nitric Oxide Synthase (ENOS) dengan Pembentukan Myofibroblast pada Model Fibrosis Ginjal Mencit (Mus Musculus) dengan Unilateral Ureteral Obstruction

FAHMI ZAHWAN KHINANA, dr. Nur Arfian, Ph.D.; dr. Santosa Budiharjo, M. Kes. , PA (K)

2014 | Skripsi | PENDIDIKAN DOKTER

Latar Belakang: Fibrosis ginjal merupakan kondisi akhir dari gagal ginjal dan penyakit ginjal kronis. Karakteristik yang muncul berupa glomerulosklerosis dan fibrosis intersisial yang diikuti pembentukan serta aktivasi myofibroblast. eNOS berperan dalam proses fibrosis ginjal dan penyakit ginjal, penurunan produksi eNOS dapat mengakibatkan percepatan progresi penyakit ginjal. Tujuan: Tujuan penelitian ialah mengamati ekspresi eNOS pada keadaan fibrosis ginjal serta mengamati korelasi antara ekspresi eNOS dan pembentukan myofibroblast. Metode: Subjek penelitian berupa mencit swiss, jantan, 2-3 bulan, 30-40 gram. Subjek dibagi menjadi tiga kelompok, yaitu kelompok Sham, UUO7, dan UUO14. Terminasi dilakukan pada hari ke 7 dan 14 setelah perlakuan. Eskpresi eNOS diperoleh dengan RT-PCR dan fraksi area pembentukan myofibroblast diamati melalui software imageJ perbesaran 400x. Hasil bermakna jika nilai p<0,05. Hasil: Terdapat peningkatan fraksi area pembentukan myofibroblast pada masing-masing kelompok (P<0,001). Pada hari ke 14 terdapat penurunan ekspresi eNOS (p<0,05) dibandingkan kelompok sham. Peningkatan myofibroblast berkorelasi negatif dengan penurunan ekspresi eNOS pada hari ke 14 setelah perlakuan. Kesimpulan: Terdapat perbedaan pembentukan myofibroblast pada ketiga kelompok serta terdapat korelasi negatif antara ekspresi eNOS dan pembentukan myofibroblast.

Background: Kidney fibrosis is a end stage of renal failure and chronic kidney diseases. It is characterized by glomerulosclerosis and intersisial fibrosis which is followed by formation and activation of myofibroblast. eNOS has been known to play role in the process of kidney fibrosis and renal disease, decreased eNOS production can lead to accelerated progression of kidney disease. Objective: The objective of this study was to observe the expression of eNOS in the state of renal fibrosis as well as observing the correlation between eNOS expression and myofibroblast formation. Method: We performed UUO in swiss background mice, male, 2-3 month, 30-40 gram. We divided into three groups: Sham group (control), d7 UUO, and d14 UUO which were sacrified in day 7 and 14 after operation. We Observe eNOS expression by RT-PCR and myofibroblast fraction area by 400x magnification of ImageJ software. Results is meaningful if the value of p <0.05. Result: There were signifance increase of myofibrobast fraction area between each group (p<0.001). In d14 of UUO, we also found a reduction of eNOS expression (p<0.05) compared to SO group. Increase of myofibroblast area was correlate with reduction of eNOS expression in d14 after UUO (p<0.05). Conclusion: There are differences in myofibroblast formation in all three groups and there is a negatif correlation between eNOS expression and myofibroblast formation.

Kata Kunci : Fibrosis, gagal ginjal kronis, myofibroblast, eNOS, unilateral ureteral obstruction (UUO).