抑制JNK信号通路对致痫后海马神经元损伤的保护作用

目的：探讨抑制C—Jun氨基末端激酶通路（JNK）对减轻癫痫持续状态（SE）大鼠海马神经元损伤的作用和机制。方法：建立氯化锂-匹罗卡品SE模型，其中24只鼠为单纯模型组；另24只鼠为抑制组，即在注射氯化锂-匹罗卡品之前，预先用特异抑制剂SP600125作侧脑室注射。另用6只鼠作正常对照，不制模，用生理盐水代替氯化锂一匹罗卡品，用二甲基亚砜（DMS0）溶液代替SP6001250。3组都在不同时间点用免疫组化法检测海马CA1区磷酸化JNK（P—JNK）的表达，并将抑制组与模型组、对照组相比较，观察组织病理学改变。结果：正常对照组JNK极少活化；模型组在SE后30min时点JNK在海马神经元强烈激活，2h时达到高峰，6h后明显减少；抑制剂组JNK激活明显减少。模型组海马CA1区可见到神经元发生变性和坏死，抑制剂组这种变化则较轻。结论：SE后JNK信号转导（transduction）通路被激活，并可致发作后海马神经元损伤；抑制剂SP600125则抑制JNK信号转导通路，对海马神经元起一定保护作用。

Protective effect of inhibition of JNK signal transduction pathway in the hippocampus of epileptogenic rat

Objective：To examine the effect and mechanism of inhibition of c -Jun amino terminal kinase（JNK） pathway in reducing the impairment of rat hippocampus in status epilepticus（SE）. Methods： The lithium-pilocarpine-induced rat models of SE were made and pretreated with SP600125,1ateral ventri cle injection, so as to evaluate the phosphorylation form of JNK by immunohistochemistry and to observe histopathologioal changes at different times after pilocarpine injection. Results：The JNK was scarcely acti rated in salin-treated rat hippocampal formation. In pilocarpine-treated rats, the hippocampal neurons showed a strong immunoreactivity of phospho JNK in CA1 neurons in 30 min,which reached the highest at the time of the 2 hours after pilocarpine injection,and then,decreased markedly 6 h later. At all points of time,activation of JNK in the model group was significantly higher than in the inhibition group. Many injured neurons were found in hippoeampus of SE rats, but obviously decreased in the inhibition group. Conclusion： JNK signal transduction pathway may be activated in lithium-piloearpine-induced model of SE,and involved in hippocampal neurons injury pathophysiology; but inhibtion of JNK may contribute to protecting the neurons against the impairment.