氯碘羟喹对癫痫小鼠海马神经元凋亡和学习记忆功能的保护作用

Protective effects of clioquinol on the hippocampal neuronal apoptosis and learning and memory functions of epileptic mice

目的研究氯碘羟喹对癫痫小鼠海马神经元凋亡和学习记忆功能的保护作用。方法采用匹罗卡品癫痫小鼠模型。实验动物根据给药方式分3组:对照组(生理盐水)、癫痫组(匹罗卡品+生理盐水)、氯碘羟喹组(匹罗卡品+氯碘羟喹)。金属自显影技术观察海马锌的分布;尼氏染色观察海马神经元形态和数量;免疫印迹检测海马Bcl-2和Bax表达;ELISA检测海马Caspases-9和Caspases-3表达;动物行为学观察自发性癫痫发作次数、发作级别和发作持续时间;T迷宫和Y迷宫检测学习记忆能力。结果氯碘羟喹组小鼠海马锌显著减少;神经元损伤减轻,细胞数量增多;Bcl-2表达增多,Bax、Caspases-9和Caspases-3表达减少,Bcl-2/Bax值增大;癫痫发作次数减少,发作级别降低,发作持续时间缩短,学习记记能力增强(P<0.01)。结论氯碘羟喹能保护小鼠海马神经元,改善学习记忆功能。

Objective To study the protective effects of clioquinol on the hippocampal neuronal apoptosis and learning and memory functions of epileptic mice.Methods The epileptic mice model were built by pilocarpine in this study.Mice were divided into 3 groups:a control group(saline),an epilepsy group(pilocarpine and saline)and a clioquinol group(pilocarpine and clioquinol).Then the distribution of zinc in hippocampus was observed by autometallography.The morphological changes and the number of neurons were checked by Nissl staining.The expression of Bcl-2 and Bax protein were detected by immunoblotting.Enzyme linked immunosorbent assay was used to check the expression of caspases-9 and caspases-3 protein.The seizure times,seizure level and seizure duration were checked by behavioral observation.The learning and memory ability was shown by T maze and Y maze.Results In the clioquinol group,the distribution of zinc in hippocampus reduced significantly,the damage of hippocampal neurons was improved and the number of neurons increased,the expression of Bcl-2 protein increased,while the expression of Bax,caspases-9 and caspases-3 protein decreased.The ratio of Bcl-2 to Bax increased.The seizure times,seizure level and seizure duration decreased.The ability of learning and memory was improved(P<0.01).Conclusions Clioquinol can protect hippocampal neurons and improve the learning and memory functions of epileptic mice.