Effect of Omi/HtrA2 inhibitor on tubular cell apoptosis induced by renal ischemia/reperfusion injury in rats

Objective To investigate the effect of UCF-101, an Omi/HtrA2 inhibitor, on tubular cell apoptosis induced by renal ischemia/reperfusion injury in rats. Methods Male Wistar rats were randomly divided into the follow ing five groups: sham group (DMSO alone), model group 1 (I/R plus DMSO before reperfusion), model group 2 (I/R plus DMSO after reperfusion), treatment group 1 (I/R plus UCF101 before reperfusion) and treatment group 2 (I/R plus UCF101 after reperfusion). Renal I/RI models were established by clamping both renal arteries for 45 min and reperfusion for 24 h. The level of serum creatinine (Scr) and blood urea nitrogen (BUN) were measured by colorimetry, protein expressions of renal cysteinyl aspartate-specific protease (caspase)-3 and caspase-9 were detected by western blotting. Tubular cell apoptosis was confirmed by terminal deoxynucleotidyl transferase (TDT)-mediated dUTP-biotin nick end labeling (TUNEL) assay. Results Renal I/R injury induced significant increases in Scr and BUN (P0.05), tubular cell apoptosis (P0.05) and protein expressions of caspase-3 and caspase-9 (P0.05). Use of UCF-101 10 min before reperfusion was found to markedly improve renal function (P0.05), decrease tubular cell apoptosis (P0.05) and the expressions of caspase-3 and caspase-9 (P0.05), while UCF-101 administered at 1 h after reperfusion did not show any effects on renal function (P0.05), tubular cell apoptosis (P0.05) and the expressions of caspase-3 and caspase-9 (P0.05). Conclusion UCF-101 appeared to suppress tubular cell apoptosis induced by renal I/R injury and protect renal function.