抑制p38/ATF2信号通路对氯化锂-匹罗卡品致癫痫大鼠海马神经元损伤的保护作用研究  

Protective Effect of Inhibition of p38/ATF2 Signaling Pathway on Hippocampal Neuron Injury in Lithium Chloride-Pilocarpine Induced Epilepsy Rats

作　　者：韩仲谋 夏杰[1] 陈静 张其梅[1] Han Zhongmou;Xia Jie;Chen Jing;Zhang Qimei(Department of Neurology,Yichang Central People's Hospital,The First College of Clinical Medical Science,China Three Gorges University,Yichang 443003,China)

机构地区：[1]三峡大学第一临床医学院[宜昌市中心人民医院]神经内科,湖北宜昌443003

出　　处：《巴楚医学》2021年第2期21-25,30,共6页Bachu Medical Journal

基　　金：湖北省自然科学基金项目(No:2016CFB345);宜昌市医疗卫生科研项目(No:A18-301-02)。

摘　　要：目的:探讨抑制p38/活化转录因子2(p38/ATF2)信号通路对癫痫持续状态(SE)大鼠海马神经元损伤的保护作用。方法:建立氯化锂-匹罗卡品致SE模型,预先用p38特异抑制剂(SB203580)侧脑室注射,在不同时间点观察海马组织形态学变化及p38、ATF2、p-p38、p-ATF2蛋白表达。结果:癫痫组大鼠海马CA1区可见神经元发生变性和坏死,抑制剂组较轻。癫痫组、抑制剂组和对照组大鼠p-p38和p-ATF2蛋白表达量增高、p-p38/p38比值和p-ATF2/ATF2比值增高,6 h时达高峰,与假手术组相比均有统计学意义(均P<0.01)。抑制剂组p-p38蛋白、p-p38/p38比值、p-ATF2蛋白、p-ATF2/ATF2比值较癫痫组和对照组均明显减少,差异均有统计学意义(均P<0.01)。结论:抑制p38/ATF2信号转导可改善SE诱导的海马神经元损伤。Objective:To investigate the protective effect of inhibition of p38/activated transcription factor 2(ATF2)signal pathway on hippocampal neuron injury in status epilepticus(SE)rats.Methods:The model of SE was induced by lithium chloride and pilocarpine.The p38 specific inhibitor(SB203580)was injected into the lateral ventricle in advance.The morphological changes of hippocampal tissue,and the protein expression of p38,ATF2,p-p38 and p-ATF2 were detected at different time points.Results:Degeneration and necrosis of neurons were occurred in the hippocampal CA1 region in the epilepsy group,while those in the inhibitor group were much slighter.The expression of p-p38 and p-ATF2 protein,as well as the ratio of p-p38/p38 and p-ATF2/ATF2 were increased with the peak at 6 h in the epilepsy group,the inhibitor group and the control group,which were significantly higher than those in the sham operation group(all P<0.01).The indicators including p-p38,p-p38/p38,p-ATF2 and p-ATF2/ATF2 in the inhibitor group were significantly lower both than those in the epilepsy group and the control group(all P<0.01).Conclusion:Inhibition of p38/ATF2 signal transduction can improve the hippocampal neuron injury induced by SE.

关 键 词：P38 ATF2 癫痫 海马神经元 

分 类 号：R965[医药卫生—药理学]