【摘要】 目的探讨白藜芦醇(Res)在氯化锂联合重复低剂量匹罗卡品诱导癫痫持续状态大鼠模型中的抗氧化作用及其机制。方法 54只SD大鼠随机分为3组:对照组、癫痫模型组和Res治疗组,采用氯化锂联合重复低剂量匹罗卡品腹腔注射制备癫痫持续状态大鼠模型,Res治疗组同时给予白藜芦醇预防性治疗。对大鼠按痫性分级标准进行行为学观测;采用化学比色法检测痫性发作90min后大鼠海马超氧化物歧化酶(SOD)、谷胱甘肽(GSH)、谷胱甘肽过氧化物酶(GSH-PX)和谷胱甘肽还原酶(GR)含量变化;采用免疫组织化学和免疫印迹法检测痫性发作90min后大鼠海马中凋亡相关蛋白Bcl-2、Caspase-3和Bax的表达变化。结果癫痫大鼠海马SOD、GSH、GSH-PX和GR的含量较对照组显著减少,凋亡相关蛋白Bcl-2表达下调,Bcl-2阳性细胞数量减少,而Caspase-3和Bax表达显著上调,Caspase-3和Bax阳性细胞数量增多。白藜芦醇预防性治疗后,大鼠痫性发作潜伏期较模型组显著延长;大脑海马中巯醇抗氧化剂(酶)SOD、GSH、GSH-PX和GR的含量明显上调;海马中抗凋亡蛋白Bcl-2表达量和Bcl-2阳性细胞数量均增加,同时促凋亡因子Caspase-3和Bax的表达被抑制,Caspase-3和Bax阳性细胞数量减少。结论白藜芦醇能通过上调癫痫模型大鼠海马内源性巯醇抗氧化剂(酶)SOD、GSH、GSH-PX和GR的含量,调控凋亡相关蛋白Bcl-2、Caspase-3和Bax的表达,对抗癫痫持续状态诱导的神经细胞氧化损伤,发挥神经保护作用。更多还原

【Abstract】 Objective To explore the antioxidatition and mechanism of the resveratrol’s in status epilepticus(SE)rat model induced by treated with LiCl plus repeated low doses of pilocarpine.Methods Fifty-four SD rats were divided into three groups at random: control group,model group and treatment group.The rat SE model was established by injecting LiCl plus repeated low doses of pilocarpine into the abdominal cavity.Meanwhile,model rats were treated by injecting peritoneally resveratrol(30mg/kg).The concentration of the thiol antioxidants,including superoxide dismutase(SOD),glutathione(GSH),glutathione peroxidase(GSH-PX) and glutathione reductase(GR),were examined by the colorimetric method in the hippocampus.The protein expression of the Bcl-2,Caspase-3 and Bax were measured using the immunohistochemistry and Western blotting technology.Results The SE model rats exhibited a significant decrease in the concentration of SOD,GSH,GSH-PX,GR and Bcl-2,while an increase in concentration of Bax,Caspase-3 and the number of positive cells compared to the control group(P<0.05).After treatment of the resveratrol,the treatment group rats exhibited significant an increase in seizure latency.Resveratrol significantly up-regulated the concentration of the thiol antioxidants(SOD,GSH,GSH-PX,GR) and increased the expression of the Bcl-2 and the number of the positive cells(P<0.05),while decreasing the expression of Caspase-3,Bax and the number of the positive cells compared to model group(P<0.05).Conclusion Resveratrol may resist the oxidative damage induced by SE,and play a neuroprotective role in the hippocampus of the SE model rat by up-regulating the concentration of thiol antioxidants(SOD,GSH,GSH-PX and GR) and regulating the apoptosis protein expression(Bcl-2,Caspase-3 and Bax).更多还原