戊四唑致痫大鼠脑内缝隙连接的作用  

Role of gap junction in pentylenetetrazol-induced epilepsy in rats

作　　者：赵秀鹤[1] 曹丽丽[1] 王胜军[1] 张同霞[1] 刘学伍[1] 迟兆富[1] 

机构地区：[1]山东大学齐鲁医院神经内科,山东济南250012

出　　处：《中国病理生理杂志》2012年第1期118-123,共6页Chinese Journal of Pathophysiology

基　　金：山东省优秀中青年科学家科研奖励基金资助项目(No.2007BS03022)

摘　　要：目的:研究缝隙连接(gap junction,GJ)在癫痫发病中的作用及机制。方法:以戊四唑(pentylene-tetrazol,PTZ)致痫大鼠模型为研究对象,采用免疫组织化学和实时定量RT-PCR技术,分别检测缝隙连接蛋白Cx32和Cx43在癫痫发作后不同时点皮层和海马神经元的表达。加用卡马西平(carbamazepine,CBZ)和甘珀酸(carbenoxolone,CBX)干预,观察二者对Cx32/43表达以及大鼠癫痫发作的影响。结果:免疫组织化学染色显示PTZ致痫2 h后大鼠脑内Cx32/43阳性细胞开始增多,8 h后增多更为明显。实时定量RT-PCR示致痫2 h Cx32mRNA迅速升高,5 h达高峰。Cx43 mRNA表达水平较低,但明显高于对照组。CBX显著抑制了Cx32/43的表达,CBZ对Cx32和Cx43的表达无明显影响。二者均抑制了大鼠的痫样发作。结论:GJ参与癫痫的发病过程,具有促进癫痫发作的作用。CBZ不影响Cx32/43的表达,表明其抗癫痫作用机制与阻断GJ无关。AIM： To study the role of gap junction（GJ） in the pathogenesis of epilepsy.METHODS： The expression of connexin（Cx） 32 and Cx43 was evaluated in penlylenetetrazol（PTZ）-induced epilepsy rats at different time points with immunohistochemistry and real-time RT-PCR.The uncoupler of gap junction,carbenoxolone（CBX）,and anti-epilepsy drug,carbamazepine（CBZ）,were introduced to investigate the role of gap junction in epilepsy.RESULTS： The expression of Cx32 in the cortex and hippocampus of rats increased 2 h after PTZ administration,and was more obvious 8 h later,so was the expression of Cx43.CBX not only notably inhibited the expression of Cx32 and Cx43,but also suppressed the seizures.CBZ had no obvious effect on Cx32/43 expression.Real-time RT-PCR examination showed that the level of Cx32 mRNA went up rapidly 2 h after seizures,and began to decrease 10 h later.The level of Cx43 mRNA in PTZ group was higher than that in control group from 2 h to 5 h.CBX inhibited both the seizures and the increase in the mRNA expression of Cx32/43,while CBZ only suppressed the seizures and did not affect the expression of Cx32/43.CONCLUSION： GJ between neurons is reinforced after epileptic activities and takes part in the pathophysiological mechanism of synchronization and epilepsy.CBZ has no effect on the expression of Cx32 and Cx43,indicating that the anti-epileptic mechanism of CBZ is independent of GJ.

关 键 词：癫痫 缝隙连接 卡马西平 甘珀酸 戊四唑 

分 类 号：R742.1[医药卫生—神经病学与精神病学]