【摘要】 目的:探讨他克莫司对大鼠肾缺血再灌注(I/R)损伤的保护作用及机制。方法:将60只健康雄性Wistar大鼠随机分为3组:假手术组、I/R组和他克莫司处理组,每组各4个时点(0.5 h、2 h、6 h、24 h)。建立肾I/R损伤模型;检测各组大鼠血清肌酐(Cr)、肿瘤坏死因子(TNF-α)、丙二醛(MDA)含量及超氧化物歧化酶(SOD)活性;用光学显微镜观察各组大鼠肾组织病理变化;用免疫组化法检测Fas和caspase-3蛋白的表达。结果:在相应再灌注各时点,他克莫司处理组血清Cr、TNF-α和MDA水平均低于I/R组(P<0.05),而他克莫司处理组血清SOD活性高于I/R组(P<0.05)。他克莫司处理组肾组织损伤程度明显轻于I/R组。与假手术组比较,I/R组凋亡蛋白Fas和caspase-3表达水平显著增加(P<0.05),而他克莫司处理组凋亡蛋白Fas和caspase-3表达水平则低于I/R组(P<0.05)。结论:他克莫司能有效抑制I/R引起的自由基产生、肾小管上皮细胞凋亡以及TNF-α水平降低,表明他克莫司对大鼠肾I/R损伤具有保护作用。更多还原

【Abstract】 AIM: To investigate the protective effects and mechanism of tacrolimus on renal ischemia/reperfusion(I/R) injury in rats. METHODS: Sixty male Wistar rats were randomly divided into 3 groups: sham-operated group,I/R group and tacrolimus group.After the renal I/R injury model was established,the serum content of creatinine(Cr),tumor necrosis factor-α(TNF-α)and malondialdehyde(MDA) and activity of superoxide dismutase(SOD) were measured at reperfusion time points of 0.5 h,2 h,6 h and 24 h.The renal histopathological lesions and the expression of Fas and caspase-3 were observed by the methods of microscopy and immunohistochemistry,respectively. RESULTS: At all the 4 time points,the levels of Cr,TNF-α and MDA in tacrolimus group were lower than those in I/R group(P<0.05).The SOD activity in tacrolimus group was higher than that in I/R group.Compared with I/R group,the renal histopathological lesions were improved,and the levels of Fas and caspase-3 were significantly decreased in tacrolimus group(P<0.05). CONCLUSION: Tacrolimus inhibits the production of free radical,the expression of TNF-α and apoptosis of renal tubular epithelial cells in renal I/R injury in rats,indicating that tacrolimus has protective function against renal I/R injury.更多还原