唑尼沙胺对癫痫小鼠学习记忆及海马神经元的影响

摘要

目的 探讨应用唑尼沙胺对癫痫小鼠空间学习、记忆能力的影响,并观察海马组织形态学的改变.方法 60只小鼠随机分为正常对照组和模型组,模型组采用腹腔注射戊四氮(45 mg/kg)复制癫痫动物模型.筛选造模合格小鼠30只随机分为癫痫模型组、唑尼沙胺组,各15只.正常对照组、癫痫模型组每日经口腔灌胃0.9%的氯化钠溶液0.15 ml,唑尼沙胺组经口腔灌胃溶于0.9%氯化钠溶液的唑尼沙胺(75 mg/kg).观察各组小鼠行为表现,2周后行Morris水迷宫实验5 d,结束后取海马组织切片行HE染色,光学镜下观察海马组织形态学变化.结果 与癫痫模型组比较,唑尼沙胺组在定位航行和空间探索时间均有明显提升,差异有统计学意义(P0.05);且唑尼沙胺能够减轻海马神经元细胞损伤.结论 唑尼沙胺能够延长惊厥发作潜伏期,缩短发作持续时间,减少自发发作次数,降低致痫小鼠的惊厥发作级别,进而减轻脑组织神经元损伤程度,改善癫痫小鼠的认知功能.%Objective To investigate the effect of Zonisamide on the learning and memory and hippocampal neurons in epilepsy mice.Methods 60 mice were randomly divided into normal control group and model group.Epilepsy animal model was reproduced by intraperitoneal injection of pentylenetetrazole (45 mg/kg).Screening of qualified mice were randomly divided into epilepsy model group, zonisamide group and 15 rats.Normal control group, epilepsy model group were daily orally administrated with 0.9% sodium chloride solution 0.15 ml.The zonisamide group was orally administrated with zonisamide (75 mg/kg) dissolved in 0.9% sodium chloride solution.Morris water maze was observed after 2 weeks.After 5 days, the hippocampal tissue sections were stained with HE and the morphological changes of hippocampus were observed under light microscope.Results Compared with epilepsy group, the navigation and time space exploration in Zonisamide group were statistically difference (P0.05).And zonisamide could reduce hippocampal neuron damage.Conclusion Zonisamide is able to extend the seizure incubation period, can shorten the duration, reduce the frequency of spontaneous and reduce level of seizure epilepsy induced mice, reduce brain damage in neurons, improve cognitive function in epilepsy in mice.