NLRP3炎症小体在癫痫发病机制中的作用研究  

Research of NLRP3 inflammasome on the epilepsy pathogenesis

作　　者：张海清[1] 孔庆霞[1] 

机构地区：[1]济宁医学院附属医院神经内科,山东济宁272000

出　　处：《中风与神经疾病杂志》2014年第10期913-916,共4页Journal of Apoplexy and Nervous Diseases

基　　金：国家自然科学基金;面上项目(81371423)

摘　　要：目的检测大鼠癫痫模型急性期海马中NLRP3炎症小体表达水平,探讨NLRP3炎症小体与癫痫发作急性期的相关性及其在癫痫发病机制中的作用。方法将60只大鼠随机分为致痫后24 h、48 h、72 h、7 d及正常对照组,以氯化锂-匹罗卡品建立癫痫动物模型。应用蛋白质免疫印记法(Western blot)和荧光定量PCR(RTPCR)检测各组大鼠不同时间点海马组织中NLRP3、caspase-1、ASC表达变化,另外采用酶联免疫吸附法(ELISA)测定各组海马组织中IL-1β含量以及免疫荧光染色观察海马CA3区胶质细胞活化情况。结果模型组造模成功率75%;与对照组相比,在各时间癫痫大鼠模型中,海马组织中NLRP3、caspase-1、ASC及血清中IL-1β水平明显高于正常对照组,具有统计学意义(P<0.05);模型建立后NLRP3炎症小体各部分均随时间变化表达逐渐升高,并于72 h达高峰;血清IL-1β水平与海马NLRP3含量呈正相关(P<0.05);造模后7 d观察海马CA3区星形胶质细胞、小胶质细胞明显活化(P<0.05)。结论在癫痫发作急性期,NLRP3炎症小体被激活,推测NLRP3介导的炎症反应可能参与癫痫的发病过程。Objective To detect the expression of NLRP3 inflammasome in rat hippocampus with acute epilepsy and explore the role of NLRP3 inflammsome in epilepsy. Methods The rats were randomly divided into the control group and24 h、48 h、72 h、7 d groups post seizures. Epilepsy model was induced in rats by lithium chloride-pilocarpine. Western blot and RT-PCR technique were used to measure the expression of NLRP3,caspase-1 and ASC in hippocampus at different point of time after seizures induced,additionally ELISA was applied to assess the serum level of IL-1β and immunofluorescence staining were selected to observe the activation of gliocyte in hippocampus CA3 region. Results The success rate of epileptic molding was 75%. The level of NLRP3,ASC,caspase-1 in hippocampus and IL-1β in serum of experimental groups were higher than that of control group（ P〈0. 05）,and parts of NLRP3 inflammasome were increased gradually over time and reached the peak at 72 hour. The correlative analysis showed that there was a positive correlation between IL-1βand NLRP3. And the gliocyte in hippocampus CA3 region of 7 d post seizures were obviously activated compared with control group（ P〈0. 05）. Conclusions The NLRP3 inflammasomes are activated in rat hippocampus with acute epilepsy induced by lithium-pilocarpine. NLRP3 inflammasome mediated inflammatory response probably involved in the process of epilepsy.

关 键 词：匹罗卡品 癫痫 NLRP3炎症小体 IL-1Β 

分 类 号：R742.1[医药卫生—神经病学与精神病学]