NDRG2通过Hes1参与癫痫发作后海马齿状回的神经发生  

NDRG2 involved in neurogenesis of dentate gyrus through HES1 in epileptic seizure mouse

作　　者：刘霞 金芃芃 侯双兴 涂志兰 储新娟 杨丹 周杭 张志鹏 Liu Xia;Jin Pengpeng;Hou Shuangxing(College of Pharmacy,Hubei University of Science and Technology,Xianning Hubei 437100)

机构地区：[1]湖北省咸宁市湖北科技学院药学院,437100 [2]上海市浦东医院科创中心 [3]上海市浦东医院神经内科

出　　处：《卒中与神经疾病》2020年第1期28-32,共5页Stroke and Nervous Diseases

基　　金：上海市浦东新区卫生和计划生育委员会重点学科群项目(PWZxq2017-09);上海市浦东医院引进人才项目(2015YJ-04)。

摘　　要：目的探讨N-Myc下游调节基因2(N-Myc downstream regulated gene 2,NDRG2)与癫痫发作后海马齿状回神经发生的关系。方法 C57BL/6小鼠20只,随机分为癫痫组和对照组,每组又分为癫痫造模后1和7 d两个时间点,每个时间点5只,通过蛋白免疫印迹检测癫痫后海马齿状回NDRG2蛋白相对表达水平和mRNA相对表达水平变化;使用双皮质素(DCX)染色标记未成熟神经元,神经巢蛋白(Nestin)标记神经干细胞,神经核蛋白(NeuN)标记成熟神经元,观察NDRG2对海马齿状回神经干细胞增殖影响;采用RT-PCR检测发状分裂相关增强子1(hairy and enhancer of split 1,Hes 1)、NDRG2 mRNA相对表达表达水平,并分析两者之间的相关性;观察NDRG2参与癫痫发作后神经发生的可能机制。结果癫痫组与对照组比较,DCX、Nestin、NeuN、Hes1、NDRG2蛋白相对表达水平在1和7 d这2个时间点有显著性增高,并随时间逐渐递增。结论癫痫发作后海马NDRG2蛋白相对表达水平增高,与癫痫发作后海马齿状回的神经细胞增值时间具有一致性和相关性,NDRG2可能参与癫痫发作后海马齿状回的神经发生过程;同时发现海马NDRG2表达增加和Hes1分子表达增加具有相关性,故推测NDRG2可能通过Hes1参与癫痫发作后海马齿状回的神经发生。Objective To study the relationship between NDRG2 and hippocampal dentate gyrus neurogenesis after epileptic seizure. Methods 20 C57 BL/6 mouse were randomly divided into epileptic group and control group. Each group was divided into two groups:1 and 7 days after epileptic modeling, with 5 mouse at each time point.The expression levels of NDRG2 protein and mRNA in dentate gyrus of hippocampus after seizures were detected by Western blot. Immature neurons were labeled with DCX staining, neural stem cells were labeled with nestin and mature neurons were labeled with NeuN. The effects of NDRG2 on the proliferation of neural stem cells in dentate gyrus of hippocampus were observed. The correlation of Hes1,NDRG2 mRNA expression levels was detected by RT-PCR, and the possible mechanism of NDRG2 involved in neurogenesis after epileptic seizure was observed. Results Compared with the control group, the expression levels of DCX,Nestin,NeuN,Hes1,NDRG2 protein in the epileptic group increased significantly at the 1 st and 7 th day, and gradually increased with time. Conclusion The increase of hippocampal NDRG2 protein expression level after epileptic seizures was consistent and correlated with the increment time of hippocampal dentate gyrus after epileptic seizures.NDRG2 might be involved in the neurogenesis of hippocampal dentate gyrus after epileptic seizures. At the same time,it was found that there was a correlation between the increased expression level of NDRG2 in hippocampus and the increase in the expression level of Hes1 molecules, so it was speculated that NDRG2 might be involved in the neurogenesis of dentate gyrus after epileptic seizures through Hes1.

关 键 词：癫痫 神经发生 N-Mcy下游调节基因2 齿状回海马 发状分裂相关增强子1 

分 类 号：R742.1[医药卫生—神经病学与精神病学]