白藜芦醇对肾脏缺血再灌注损伤大鼠的保护作用及机制研究

摘要

目的 研究白藜芦醇(resveratrol,Res)对肾脏缺血再灌注损伤大鼠的保护作用并探讨其可能的作用机制. 方法 采用夹闭双侧肾蒂血管45分钟的方法建立缺血再灌注肾损伤大鼠模型并给予不同剂量白藜芦醇低、中、高剂量[10、20、40 mg/(kg·d)]和银杏叶提取物[100 mg/(kg·d)]进行干预治疗(疗程14天),并另设模型组和假手术组.计算肾脏指数,生化分析法测定血清尿素氮(blood urea nitrogen,BUN)、血肌酐(serum creatinin,SCr)、尿酸(uric acid,UA)含量,HE染色法观察肾脏组织形态结构改变;比色法检测肾脏组织中抗氧化酶活性和丙二醛(malondialdehyde,MDA);TUNEL法观察细胞凋亡状况. 结果 与模型组比较发现白藜芦醇中剂量[20 mg/(kg·d)]组、白藜芦醇高剂量[40 mg/(kg·d)]组大鼠肾脏指数显著降低,血清BUN、SCr、UA含量均显著降低;肾脏组织病变明显改善,以白藜芦醇高剂量组最为显著;抗氧化酶、超氧化物歧化酶(superoxide dismutase,SOD)、过氧化氢酶(cata-lase,CAT)活性显著升高且MDA含量显著降低,其中白藜芦醇高剂量组谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)活性显著升高;肾脏组织细胞凋亡状况明显改善、白藜芦醇中、高剂量组凋亡指数(apoptosis index,AI)显著降低;上述差异均具有统计学意义(P<0.05,P<0.01). 结论 白藜芦醇能够通过抑制氧化应激和细胞凋亡而对肾脏缺血再灌注损伤大鼠起到一定的保护作用.%Objective To investigate the protective effects and mechanism of resveratrol (Res) on the rats with renal ischemic-reperfusion injury.Methods The rat models with renal ischemic-reperfusion injury were induced by clipping bilateral renal pedicle vascular for 45min and the rats were treated with Res low-dose, medium-dose and high-dose [10, 20, 40 mg/(kg·d)] and ginkgo biloba extract [EGb, 100 mg/(kg·d)] for 14d, and set model group and sham operation group.The renal index was calculated;the content of BUN, SCr, UA in serum were determined;the pathological changes of the renal tissue were observed by HE staining;the activity of antioxidase and the content of MDA in renal tissue were determined by colorimetry;the apoptosis of renal cells was observed by TUNEL staining.Results Compared with model group, the renal index in Res medium-dose and high-dose groups were significantly decreased;the content of BUN, SCr, UA in serum were significantly decreased;the pathological changes were significantly improved, especially the Res high-dose treated group;the activity of SOD, CAT in renal tissue were significantly increased and the content of MDA was significantly decreased, and the activity of GSH-Px in Res 40 mg/(kg·d) group was significantly increased;the apoptosis in Res groups were significantly improved, especially the apoptosis index in Res medium-dose and high-dose treated groups were significantly decreased;all of the difference above were significant(P<0.05, P<0.01).Conclusion Res has protective effects on the rats with renal ischemic-reperfusion injury, which perhaps related to its effects of inhibiting oxidative stress and apoptosis.