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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。
Objective To investigate the anti-oxidative effect and mechanism of resveratrol (Res) in a rat model of epilepticus induced by lithium chloride combined with repeated low-dose pilocarpine. Methods 54 Sprague-Dawley rats were randomly divided into three groups: control group, epilepsy model group and Res treatment group. Rats in epilepticus were induced by intraperitoneal injection of lithium chloride combined with repeated low-dose pilocarpine. Res treatment group was given concurrent Resveratrol prophylactic treatment. The behavioral observations of rats were made according to the criteria of seizure grade. The levels of superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidation (GSH-PX) and glutathione reductase (GR) in hippocampus of rats were detected by immunohistochemistry and Western blotting. The apoptosis-related proteins Bcl-2, Caspase-3 Bax expression changes. Results The levels of SOD, GSH, GSH-PX and GR in the hippocampus of epileptic rats decreased significantly compared with those of the control group. The expressions of Bcl-2, Bcl-2 and Bcl-2 were decreased, while the expressions of Caspase-3 and Bax were up- Caspase-3 and Bax-positive cells increased. After prophylactic treatment of resveratrol, the latent period of seizure in rats was significantly longer than that in model group. The contents of antioxidants (SOD, GSH, GSH-PX and GR) in hippocampus of hippocampus were significantly increased; The protein expression of Bcl-2 and the number of Bcl-2 positive cells were increased, while the expression of pro-apoptotic factors Caspase-3 and Bax was inhibited, and the number of Caspase-3 and Bax positive cells decreased. Conclusion Resveratrol regulates the expression of Bcl-2, Caspase-3 and Bax in the hippocampus of the epilepsy model rats by increasing the contents of antioxidative enzymes (SOD, GSH, GSH-PX and GR) Expression, antagonism of status epilepticus induced neuronal oxidative damage, play a neuroprotective role.