z-VAD-FMK对大鼠肾缺血再灌注损伤的保护作用

目的：探讨z-VAD-FMK对大鼠肾缺血再灌注损伤的影响及其机制.方法：30只雄性SD大鼠随机分为3组：假手术组、对照组（DMSO组）、给药组（z-VAD-FMK组）,每组10只.对照组和给药组大鼠采用切除右肾,夹闭左侧肾动脉45 min后再恢复血流的方法制成肾缺血再灌注模型,于模型完成前15 min尾静脉给药;假手术组只切除右肾.模型成功后24 h收集大鼠血清和肾脏组织;测定血清肌酐（Scr）、尿素氮（BUN）;HE染色观察肾组织病理改变;TUNEL检测肾细胞凋亡;ELISA检测TNF-α、IL-10浓度;Western blot检测caspase-3和caspase-8表达.结果：与对照组相比,给药组Scr与BUN水平明显降低（P＜0.01）;HE染色可见肾小管上皮细胞脱落、间质水肿、炎细胞浸润明显减少;肾小球和肾小管上皮细胞凋亡指数明显降低（P＜0.01）;TNF-α、IL-10表达水平明显降低（P＜0.01）;caspase-3和caspase-8表达明显降低（P＜0.01）.结论：z-VAD-FMK对大鼠肾缺血再灌注损伤有保护作用,其机制可能与抑制细胞凋亡,减轻炎症损伤有关.

Protective effects of z-VAD-FMK on renal ischemia-reperfusion injury in rat

Objective： To investigate the effects and the mechanism of z-VAD-FMK in renal ischemia-reperfusion injury in rat. Methods： Thirty male adult SD rats were divided randomly into 3 groups： sham group, control （DMSO） group, drug （z-VAD-FMK） treated group. The rats in control group and z-VAD-FMK group were established at 45 min after the left renal artery occlusion on the basis of the right renal resection. Drugs were given through the tail vein 15 rain before reperfusion, while the fight kidney in rats was resected in the sham group but the left artery was not clamped. Kidneys and blood samples were obtained after reperfusion to determine serum creatinine （Scr） and blood urea nitrogen （BUN）. Renal morphology dyed with HE was observed with microscope. TUNEL was used to detect the apoptosis of kidney ceils. ELISA was applied to detect the levels of TNF-ct and IL-10. Expressions of caspase-3 and caspase-8 protein were assessed by Western blot. Results：Compared with control group, plasma levels of Scr and BUN were significantly lower in the z-VAD-FMK treated group（P〈0.01）; the slough of tubular epithelial cells, the edema of interstitial and the infiltration of inflammatory cells significantly decreased; the number of apoptotic glomerular cells also significantly decreased （P〈0.01）; the expressions of TNF-α, IL-10 were significantly lower （P〈0.01）; the expressions of caspase-3 and caspase-8 protein significantly decreased（P〈0.01）. Conclusion：z-VAD- FMK can protect the renal ischemia-reperfusion injury in rat, which may be associated with the inhibition of apoptosis and inflammation.