Omi/HtrA2抑制剂对肾脏缺血再灌注损伤诱导的肾小管上皮细胞凋亡的影响

目的研究Omi/HtrA2抑制剂(UCF-101)对大鼠肾脏缺血/再灌注(I/R)损伤诱导的肾小管上皮细胞凋亡的影响。方法雄性Wistar大鼠随机分为5组:假手术组(DMSO)、模型1组(I/R+R前DMSO)、模型2组(I/R+R后DMSO)、治疗1组(I/R+R前UCF-101)和治疗2组(I/R+R后UCF-101)。双侧肾动脉夹闭45min再灌注24h制作动物模型;比色法测定血清肌酐和尿素氮浓度;Western blot法检测肾组织中天冬氨酸特异性半胱氨酸蛋白酶(caspase)-3、caspase-9的蛋白质表达;原位末端标记TUNEL法检测肾小管上皮细胞凋亡。结果肾脏缺血45min再灌注24h后,大鼠肾功能明显减退(P<0.05);肾组织中caspase-3、caspase-9蛋白质表达显著增加(P<0.05),大量肾小管上皮细胞凋亡(P<0.05)。再灌注前给予UCF-101能显著改善肾功能(P<0.05),并显著下调caspase-3、caspase-9蛋白质表达(P<0.05),减轻肾小管上皮细胞凋亡(P<0.05),而再灌注后给药不能改善肾功能及caspase-3、caspase-9蛋白质的表达(P>0.05)。结论再灌注前给予UCF-101能抑制肾脏I/R损伤诱导的肾小管上皮细胞凋亡,对肾脏I/R损伤具有保护作用。

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 UCFIO1 after reperfusion）. Renal FRI models were established by clamping both renal arteries for 45 rain and reperfusion for 24 h. The level of serum creatinine （Set） 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 （P〈O.05）, tubular cell apoptosis （P〈0.05） and protein expressions of easpase-3 and caspase-9 （P〈0.05）. Use of UCF-101 10 rain before repeffusion was found to markedly improve renal function （P〈O.05）, decrease tubular cell apoptosis （P〈0.05） and the expressions of caspase-3 and caspase- 9 （P〈0.05）, while UCF-101 administered at 1 h after reperfusion did not show any effects on renal function （P〉0.05）, tubular cell apoptosis （P〉0.05） and the expressions ofcaspase-3 and caspase-9 （P〉0.05）. Conclusion UCF-101 appeared to suppress tubular cell apoptosis induced by renal I/R injury and protect renal function.