抑制p38/p53信号通路对癫痫大鼠神经元损伤的保护作用  

Inhibited p38/p53 signaling pathway protects neuron injury in epilepsy rats

作　　者：夏杰[1] 徐小敏 张其梅[1] XIA Jie;XU Xiaomin;ZHANG Qimei(Department of Neurology,the First Clinical Medical School,China Three Gorges University,Yichang 443002,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443000

出　　处：《实用医学杂志》2021年第13期1666-1669,1673,共5页The Journal of Practical Medicine

基　　金：国家自然科学基金青年基金项目(编号:81801068);宜昌市医疗卫生科研项目(编号:A18-301-02)。

摘　　要：目的探讨p38/p53信号通路在癫痫持续状态大鼠海马神经元的活化规律,及对癫痫后神经元损伤的保护作用。方法 40只大鼠随机分为正常对照组、癫痫组、抑制剂组、二甲亚枫溶剂对照组,建立氯化锂-匹鲁卡品癫痫大鼠模型,HE染色观察大鼠海马CA1区的神经元病理改变,免疫组化染色观察p38/p-p38、p53/p-p53阳性细胞的着色情况。结果癫痫组海马CA1区可见到神经元变性、坏死,抑制剂组较轻。癫痫组各时间点p38/p-p38阳性细胞数较对照组增加,2 h达高峰,6 h后减少,抑制剂组阳性细胞数较癫痫组减少。癫痫组各时间点p53/p-p53免疫阳性细胞数较对照组增多,癫痫发作时间越长,阳性细胞数越多,抑制剂组阳性细胞数较癫痫组减少。结论 p38抑制剂对SE大鼠神经元损伤有一定保护作用,其机制与阻断p53介导的细胞凋亡通路有关。Objective To investigate the activation of p38/p53 signaling pathway in hippocampal neurons of rats with status epilepticus(SE)and its protective effect on neuron injury after epilepsy.Methods Forty rats were randomly divided into normal control group,epilepsy group,inhibitor group and dimethylsulfoxide solvent control group.A lithium chloride-pilocarpine epileptic rat model was established.HE staining was used to detect the pathological changes of neurons in hippocampal CA1 region of rats and immunohistochemical staining to observe the staining of p38/p-p38 and p53/p-p53 positive cells.Results Many degenerated and necrotic neuron cells were found in hippocampal CA1 region of SE rats,and they were obviously decreased in number in the inhibition group.The number of p38/p-p38 positive cells in the epilepsy group increased at each time point compared with the control group,reaching the peak at hour 2 and beginning to decrease at hour 6.The number of positive cells in the inhibitor group was smaller than that in epilepsy group.Across the time points,the number of p53/p-p53 positive cells in the epilepsy group at each time point was larger than that in control group;The longer seizure lasted,the number of positive cells the larger;The number of positive cells in the inhibitor group was smaller than that in the epilepsy group.Conclusion P38 inhibitor has certain protective effect on SE rat neuron injury,probably because the p53 gene-mediated apoptosis pathway is blocked in mechanism.

关 键 词：癫痫 信号通路 P38 P53 神经元 

分 类 号：R742.1[医药卫生—神经病学与精神病学]