匹罗卡品癫痫模型中海马区TREK-2钾离子通道表达变化及意义

目的:研究匹罗卡品癫痫模型中海马区TREK-2双孔钾离子通道的表达变化,初步探讨TREK-2在癫痫发病过程中的机制及意义。方法:选用成年雄性SD大鼠腹腔注射氯化锂-匹罗卡品(lithium-pilocarpine)构建癫痫模型,分别在癫痫持续状态(status epilepticus,SE)后不同时间点(6 h、1 d、3 d、1 w、2 w、4 w、8 w)提取海马组织,利用western-blot检测海马区TREK-2随时间表达变化。并用TREK-2 si RNA下调海马区TREK-2表达,进一步观察对大鼠癫痫状态的影响。结果:与对照组相比,TREK-2在诱导癫痫持续状态发作后的3d开始降低(P0.05),1 w,2 w,4 w明显降低(P0.01),8 w时仍维持在很低水平(P0.001)。在TREK-2表达下调后,大鼠癫痫潜伏时间(latent period)明显缩短,癫痫持续状态1 h 5级以上发作频率(seizure frequency)明显增加。结论:TREK-2在氯化锂-匹罗卡品致痫大鼠海马组织中表达的降低,且其下调加重癫痫状态的事实提示TREK-2参与了癫痫的发生发展过程。

Expression Changes and Meaning of TREK-2 PotassiumIon Channel in Hippocampus in Pilocarpin-induced EpilepsyModel

Objective:To investigate the expression change of K2P channel TREK-2 in hippocampus with pilocarpin-induced epilepsy, and to explore the mechanism and siginificance of epilepsy in which TREK-2 was involved.Methods:The epilepsy model was conducted by celiac injection of lithium-pilocarpine with adult male Sprague-Dawley rats, the hippocampus tissue was collected respectively at 6 h, 1 d, 3 d, 1 w, 2 w, 4 w and 8 w after the status epilepticus (SE), and the expression changes of TREK-2 in hippocampus was detected at different time points with Western-Blot. The expression of TREK-2 was down-regulated in hippocampus with TREK-2 siRNA, and the effect on status epilepticus (SE) was further observed.Results:Compared to control group, the expression of TREK-2 began to decrease at 3 d (P < 0.05), decreased significantly at 1 w, 2 w, 4 w, (P< 0.01), and remained a very low level at 8 w (P < 0.001). After the expression of TREK-2 declined, the latent period of epilepsy decreased significantly, and the seizure frequency of SE significantly increased within 1 h above magnitude 5.Conclusion:The decreased expression of TREK-2 potassium ion channel in hippocampus in pilocarpin-induced epilepsy model and the down-regulated TREK-2 which aggravated the status epilepticus indicated that TREK-2 participated in the ocurrence and development of epilepsy.