5-HTR6参与氯化锂-匹罗卡品致慢性颖叶癫痫大鼠海马苔藓纤维出芽的机制  

5-HTR6 involves in mossy fiber sprouting( MFS) in Lithium-pilocrapine induced epileptic rats

作　　者：黄文立 洪全龙[1] 吴志生[1] 宫淑杰[1] HUANG Wenli;HONG Quanlong;WU Zhisheng(Department of Neurology , Quanzhou First Hospital Affiliated to Fujian Medical University,Quanzhou (362000) ,Fujian , China)

机构地区：[1]福建医科大学附属泉州第一医院神经内科,福建泉州362000

出　　处：《癫痫与神经电生理学杂志》2019年第5期263-268,共6页Journal of Epileptology and Electroneurophysiology(China)

摘　　要：目的:探讨5-HTR6参与氯化锂-匹罗卡品致慢性额叶癫痫大鼠海马苔藓纤维出芽的机制。方法:动物分组:分为空白组及癫痫组,分别于造模后1、2、4周观察苔藓纤维出芽变化及5-HTR6、Fyn、p-ERK1/2蛋白及GAP-43 mRNA表达变化.将实验鼠分为空白组、癫痫组、药物干预组,药物干预组又分为6个亚组,分别给予溶剂二甲基亚砜DMSO、5-HTR6受体拮抗剂SB271046、Fyn 拮抗剂 PP2、ERK1/2 拮抗剂 PD98059、SB271046 + PP2、SB271046 + PD98059,观察海马苔藓纤维出芽及5-HTR6、Fyn、p-ERK1/2、GAP-43mRNA表达变化。结果:①造模后第2周进入慢性期,在造模后7-28 d开始出现慢性自发性发作,5-HTR6受体拮抗剂SB-271046能够降低癫痫发作等级及发作频率;②癫痫发作后1周即观察到少量海马CA3区苔藓纤维出芽,随时间延长进行性增加,而空白组未见或只有极少量海马苔藓纤维出芽。SB-271046干预后海马苔藓纤维出芽明显减少,与空白组比较差异有统计学意义;③造模后5-HTR6、Fyn、p-ERK1/2及GAP-43 mRNA表达水平增高,于造模后4周时表达最高,给予5-HTR6受体、Fyn、ERK1/2拮抗剂后p-ERK1/2表达均减少,其中联合应用5-HTR6受体、ERK1/2受体拮抗剂最为明显。结论:氯化锂-匹罗卡品点燃的大鼠癫痫模型痫样放电后出现苔藓纤维出芽,随时间延长出芽程度加重,5-HTR6可能在苔藓纤维出芽过程中发挥重要作用。而SB271046通过抑制5-HTR6介导的Fyn/ERK通路.调控下游GAP-43mRNA表达,从而减少苔群纤维出芽。Objective: To observe the mechanism of 5-HTR6 involved in mossy fiber sprouting (MFS) in Lithium-pilocapine to induce epiletptic rats. Methods: The rats involved in the experiment were divided into the normal group and the epileptic group. The changes of bryophytic fiber bud and 5- HTR6, Fyn, p-erkl/2 protein and GAP-43 mRNA expression 1, 2 and 4 weeks after modeling were observed respectively. The normal group, the epileptic group, the drug intervention group and the drug intervention group were divided into 6 subgroups. Solvent dimethylsulfoxide DMSO,5-HTR6 receptor antagonist SB271046, Fyn antagonist PP2, erk1/2 antagonist PD98059, SE271046 + PP2, SB271046 + PD98059 were respectively given to observe the changes in the expression of hippocampal mossy fiber and 5-htr6, Fyn, p-erk1/2, and GAP 43mRNA. Results: In the 4th week after SE, over expressed HTR6 and MFS became more and more obvious compared with the control group and peaked, and Levels of 5-HTR6, Fyn, p-ERK1/2 and GAP-43 mRNA increased in the same pattern as MFS. The antagonists of 5-HTR6, Fyn and p-ERK1/2 reversed MFS and reduced the expression of p- ERK1/2 and GAP-43 mRNA. Interestingly, SB271046 adding PPI orPD98059 further reversed and the latter to the most extend. Conclusion: Over-expressed HTR6 and obvious MFS in pilocarpine-induced chronic epileptic rats were observed and the expression of HTR6 may be involved in the progression of MFS through activating p-ERK1/2 via Fyn-dependant pathway modulating GAP-43 expression.

关 键 词：癫痫 5-HTR6 海马苔藓纤维出芽 FYN ERK1/2 GAP-43 

分 类 号：R742.1[医药卫生—神经病学与精神病学]