CORRELATION BETWEEN ENDOTHELIN CONVERTING ENZYME-1 EXPRESSION AND RENAL TUBULAR INJURY IN 5/6 SUBTOTAL NEPHRECTOMIZED MICE

ANDREA NUR SABRINA, dr. Nur Arfian, P.hD; dr. Dian Prasetyo Wibisono, M.Sc

2016 | Skripsi | S1 PENDIDIKAN DOKTER

LATAR BELAKANG: Penyakit Ginjal Kronis (CKD) adalah hilangnya progresif fungsi ginjal, prevalensinya meningkatkan selama bertahun-tahun. Untuk mempelajari perkembangan CKD, kita menggunakan model 5/6 subtotal nefrektomi. Pengurangan bagian ginjal akan menyebabkan cedera tubular. Cedera Tubular ditandai dengan tubular fibrosis, penipisan brush border, dan sel-sel epitel atenuasi. Fibrosis tubular diproduksi oleh Endotelin-1 (ET-1) melalui perantaraan endotelin Converting Enzyme-1 (ECE-1). TUJUAN: Untuk melihat korelasi antara ECE-1 ekspresi dan cedera tubulus ginjal di tikus dengan 5/6 subtotal nefrektomi. METODE: tikus galur Swiss usia 3-4 bulan yang dihilangkan 5/6 bagian dari ginjal, dalam tujuan untuk memberikan CKD model. Tikus kemudian dikorbankan dalam 3 kelompok yang berbeda waktu: 1) kelompok operasi sham / kontrol, 2) 7 hari setelah 5/6 SN, dan 3) 28 hari setelah 5/6 SN. sampel kemudian dikumpulkan dan diukur untuk ECE-1 dan cedera tubular untuk melihat perkembangan CKD. Ekspresi ECE-1 diukur dengan menggunakan Reverse Transcriptase- Polymerase Chain Reaction (RT-PCR), sementara scoring Cedera Tubular diukur secara histopatologi kadar dengan Periodic Acid Schiff (PAS) stain. HASIL: Cedera Tubular scoring meningkat secara signifikan antara masing-masing kelompok (p <0,05). Tingkat ekspresi ECE-1 meningkat pada kelompok 7 hari dan menurun pada 28 hari kelompok, dengan analisis data statistik menunjukkan hasil tidak signifikan (p> 0,05). Uji korelasi Pearson menunjukkan hasil statistik tidak signifikan (p> 0,05), yang berarti tidak ada korelasi antara peningkatan kerusakan tubulus ginjal dan tingkat ECE-1 ekspresi. KESIMPULAN: Dalam percobaan ini, Cedera Tubular meningkat sementara ekspresi ECE-1 tidak meningkat. Ada banyak faktor yang dapat berkontribusi pada penurunan ECE-1. Hal ini dapat menyebabkan ekspresi ECE-1 tidak memiliki korelasi dengan peningkatan Cedera Tubular di tikus dengan 5/6 subtotal nefrektomi.

BACKGROUND: Chronic Kidney Disease (CKD) is a progressive loss of kidney function, the prevalence is increasing over the years. To study the progression of CKD, we use 5/6 subtotal nephrectomy model. The reduction of kidney parts will cause tubular injury. Tubular injury is characterized by tubular fibrosis, depletion of brush border, and epithelial cells attenuation. Tubular fibrosis is produced by Endothelin-1 (ET-1) through the mediation of Endothelin Converting Enzyme-1 (ECE-1). OBJECTIVE: To see the correlation between ECE-1 expression and renal tubular injury in 5/6 subtotal nephrectomized mice. METHOD: Swiss-background mice age 3-4 months with removed 5/6 parts of the kidney, in purpose to give CKD model. The mice then sacrificed in 3 different groups of time: 1) sham operation/control group, 2) 7 days after 5/6 SN, and 3) 28 days after 5/6 SN. The samples were then collected and measured for ECE-1 expression and tubular injury to see the progression of CKD. ECE-1 expression was measured using Reverse Transcriptase- Polymerase Chain Reaction (RT-PCR), while Tubular Injury scoring was measured using histopathological grading with Periodic Acid Schiff (PAS) stain. RESULT: Tubular Injury scoring increased significantly between each group (p<0.05). ECE-1 expression level increased in 7 days group and declined in 28 days group, with statistical data analysis showing nonsignificant result (p>0.05). Pearson correlation test showed statistically insignificant result (p>0.05), meaning there was no correlation between increased damage of renal tubules and the level of ECE-1 expression. CONCLUSION: In this experiment, Tubular Injury scoring was increased while ECE-1 expression was not increased. There are many factors that can contribute to the decrease of ECE-1 expression. This may cause ECE-1 expression to have no correlation with the increase of Tubular Injury scoring in 5/6 subtotal nephrectomized mice.

Kata Kunci : KEYWORDS: chronic kidney disease, tubular injury, endothelin-1, endothelin converting enzyme-1, subtotal nephrectomy.