Olomoucine在匹罗卡品所致颞叶癫痫间中的作用及机制的研究  

Effects and mechanisms of olomoucine on temporal lobe epilepsy

作　　者：殷亚萍[1] 刘希金[1] 杨志勇[1] 邓学军[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院神经内科,武汉430022

出　　处：《卒中与神经疾病》2013年第4期195-199,共5页Stroke and Nervous Diseases

摘　　要：目的研究细胞周期依赖激酶(CDK)抑制剂在氯化锂-匹罗卡品(Licl-Pilocarpine)所致颞叶癫痫间大鼠痫间性发作中的作用及其相关机制。方法用Licl-Pilocarpine制作大鼠颞叶癫痫间模型;用CDK抑制剂Olomoucine在大鼠癫痫间持续状态后第3、4、5 d进行干预,并将参与实验的大鼠分为正常组、模型组、干预组和对照组;用视频监测各组大鼠的癫痫间发作情况,记录距离第1次慢性自发性发作的潜伏期、慢性自发性发作的频率及贯穿于整个过程中大鼠的病死率;用脑电图监测各组出现慢性自发性发作大鼠的脑电活动的变化,记录发作间期棘波发放的情况;用免疫组化检测GFAP(胶质纤维酸性蛋白,一种星形胶质细胞的标记物)和ADK(腺苷激酶)的表达水平。结果干预组较模型组距第1次发作的潜伏期明显延长,临床发作次数明显减少,棘波发作的频率和持续时间明显缩短(P<0.05);GFAP和ADK的表达量明显下降(P<0.05);模型组较正常组GFAP和ADK的表达量明显增加;对照组较模型组无明显变化。结论 CDK抑制剂在一定程度上能够减少癫痫间大鼠的痫间性发作次数和脑电波的棘波发放,其机制可能为细胞周期依赖激酶抑制剂能够抑制星形胶质细胞的增生,减少ADK的表达,间接的增加了内源性止痫间剂腺苷的含量。Objective To investigate the correlation between temporal lobe epilepsy （TLE） and cell cy- cle inhibition through pilocarpine-induced rat models of temporal lobe epilepsy and surgical samples of temporal neocortex from intractable epilepsy patients. Methods Olomoucine （a CDK inhibitor） was used at an acute stage of induced TLE. Behavioral changes and electroencephalogram （EEG） were interpreted after interven- tion- We also used immunohistochemistry （IHC） to detect the expression of glial fibrillary acidic protein （GFAP） and adenosine kinase （ADK）. Results We found that the frequency of seizures and the expression of GFAP and ADK were attenuated in olomoucine-treated group. What＇s more, compared with non-epileptic hu- man brain tissue, the expression of ADK was significantly increased in the epileptic human brain. Conclusions These results suggest that certain cell cycle inhibition may improve epilepsy to some extent by inhibiting as- trog[iosis and the subsequent over expression of ADK. Our paper also suggests that astrocyte-specific cell cycle inhibition may be considered as a promising therapeutic intervention for epilepsy.

关 键 词：Licl-Pilocarpine 颞叶癫痫间 CDK OLOMOUCINE 胶质细胞增生 

分 类 号：R742.1[医药卫生—神经病学与精神病学]