PENGARUH CEDERA ISKEMIA REPERFUSI GINJAL TERHADAP REMODELING PEMBULUH DARAH SERTA EKSPRESI ENDOTHELIN- 1 (ET-1) DAN ENDOTHELIAL NITRIC OXIDE SYNTHASE (eNOS) PADA MENCIT

PRATIWI INDAH SAYEKTI, dr. Nur Arfian, Ph.D; dr. Dian Prasetyo Wibisono, M.Sc.

2016 | Skripsi | S1 PENDIDIKAN DOKTER

Latar belakang: Cedera ginjal akut mengalami peningkatan insidensi yang disertai dengan angka kematian di seluruh dunia. Selain angka kematian yang tinggi, pasien dapat mengalami komplikasi berupa Penyakit Ginjal Kronis dan End-Stage Renal Disease. Endothelin-1 dan endothelial nitric oxide synthase berperan dalam proses cedera ginjal iskemia reperfusi yang disertai dengan remodeling pembuluh darah. Tujuan: Mengetahui pengaruh cedera iskemia reperfusi ginjal terhadap remodeling pembuluh darah, ekspresi ET-1, dan ekspresi eNOS. Metode: Dilakukan klem hilus renalis pada 15 ekor mencit jantan galur Swiss umur 3-4 bulan selama 30 menit. Hewan coba dikelompokkan menjadi 3 kelompok secara acak, yakni kelompok IR1 (n=5), IR12 (n=5), dan Sham Operation (SO, n=5). Remodeling vaskular dinilai dengan area lumen dan ketebalan dinding; ekspresi ET-1 dan eNOS dengan PCR. Analisis dengan uji one way ANOVA dengan post-hoc LSD. Level signifikan pada p<0,05. Hasil: Didapatkan penurunan signifikan diikuti peningkatan signifikan area lumen (SO vs IR1 p=0,003; SO vs IR12 p=0,170; IR1 vs IR12 p=0.039). Terdapat peningkatan ketebalan dinding arteri tidak signifikan diikuti penurunan signifikan (SO vs IR1 p=0,076; SO vs IR12 p=0,323; IR1 vs IR12 p=0,012). Ekspresi ET-1 mengalami kenaikan signifikan lalu menurun signifikan (SO vs IR1 p=0,001; SO vs IR12 p=0,125; IR1 vs IR12 p=0,035). Ekspresi eNOS mengalami kenaikan di IR1 dan turun di IR12, namun perubahannya tidak signifikan. Kesimpulan: Pada cedera iskemia reperfusi, terjadi remodeling pembuluh darah yang salah satu penyebabnya adalah peningkatan ekspresi ET-1. Ekspresi eNOS diyakini berperan sebagai mekanisme adaptasi terhadap cedera vaskuler sehingga arsitektur vaskuler dapat mengalami perbaikan.

Background: The incidence of acute kidney injury increased over time with increased mortality and complication, such as chronic kidney failure and end- stage renal disease. Endothelin-1 and eNOS have been known to play role in ischemic reperfusion injury followed by vascular remodeling. Objective: The aim of this study is to examine the pattern of vascular remodeling, ET-1 expression, and eNOS espression in ischemic reperfusion injury model. Methods: We performed bilateral pedicle clamping in mice with Swiss background (3-4 months old, 30-40 grams, n=15) for 30 minutes except for control group. Five mice was allocated in each group. Sham operation group (SO, n=5) served as control. Mice were sacrificed in day 1 (IR1, n=5) and day 12 (IR12, n=5) after operation. Lumen area of artery and wall thickness were observed for vascular remodeling. ET-1 and eNOS expression were examined by RT-PCR. We did statistical analysis with ANOVA and post-hoc LSD with level of significance p<0,05. Results: There were significant decrease followed by signifiant increase of lumen area (SO vs IR1 p=0,003; SO vs IR12 p=0,170; IR1 vs IR12 p=0.039) and significant increase followed by significant decrease of wall thickness (SO vs IR1 p=0,076; SO vs IR12 p=0,323; IR1 vs IR12 p=0,012). Endothelin-1 expression was increased significantly then decreased significantly (SO vs IR1 p=0,001; SO vs IR12 p=0,125; IR1 vs IR12 p=0,035). Expression of eNOS was increased then decreased in day 1 and 12 respectively however statistically not significant. Conclusion: There is vascular remodeling in acute kidney injury contributed by ET-1. Expression of eNOS serves as adaptation to microvascular injury so the damage can be kept at minimal to ensure recovery.

Kata Kunci : cedera ginjal akut, cedera iskemia reperfusi, remodeling pembuluh darah, ET-1, eNOS, acute kidney injury, ischemic reperfusion injury, vascular remodeling