癫痫持续状态下幼年癫痫大鼠海马区星形胶质细胞:大麻素2型受体调控MAPK通路的作用  

Hippocampal astrocytes in juvenile rats with persistent epilepsy:the role of cannabinoid receptor type 2 in regulating MAPK pathway

作　　者：曹庆隽[1] 杨凤华[1] 王华[1] Cao Qingjun;Yang Fenghua;Wang Hua(Department of Pediatric Neurology in Shengjing Hospital of China Medical University,Shenyang 110004,Liaoning Province,China)

机构地区：[1]中国医科大学附属盛京医院小儿神经内科,辽宁省沈阳市110004

出　　处：《中国组织工程研究》2020年第32期5179-5185,共7页Chinese Journal of Tissue Engineering Research

基　　金：辽宁省科学技术计划(2014225007),项目负责人:王华。

摘　　要：背景:星形胶质细胞增生是癫痫的重要形态学改变,增生的胶质细胞可产生细胞因子,继而激活JAK/STAT信号转导进一步促进胶质细胞的增生,从而影响癫痫的发生及复发,星形胶质细胞和信号转导途径相互影响,在癫痫的发病中发挥重要作用。目的:探讨大麻素2型受体对癫痫持续状态幼年大鼠星形胶质细胞和MAPK通路ERK、p38、JNK蛋白激活的影响。方法:健康雄性SD大鼠40只(18-21 d龄),随机分为4组:正常对照组、癫痫模型组、大麻素2型受体激动剂JWH133组、大麻素2型受体拮抗剂AM630组,正常对照组仅给予生理盐水,其他各组大鼠腹腔注射氯化锂和匹鲁卡品建立癫痫模型,并分别进行不同干预。发生癫痫持续状态后24 h取脑组织,采用免疫荧光检测海马组织GFAP与p-ERK、p-p38、p-JNK的共表达,Real-time PCR检测海马组织GFAP mRNA的表达。结果与结论:①癫痫模型组GFAP/p-ERK、GFAP/p-p38共表达较正常对照组增多(P<0.05),JWH133组较癫痫模型组减少(P<0.05),AM630组较JWH133组增多(P<0.05);②癫痫模型组GFAP/p-JNK共表达较正常对照组减少(P<0.05),JWH133组较癫痫模型组增多(P<0.05),AM630组较JWH133组减少(P<0.05);③癫痫模型组GFAP的m RNA表达较正常对照组减少(P<0.05),JWH133组较癫痫模型组有明显增多(P<0.05),而AM630组GFAP的表达降低(P<0.05);④结果表明,大麻素2型受体可以通过调控MAPK通路ERK、p38、JNK蛋白,从而影响癫痫持续状态下幼年癫痫大鼠海马区星形胶质细胞。BACKGROUND:Astrocyte proliferation is an important morphological change in epilepsy.Proliferated glial cells can produce cytokines,and in turn activates JAK/STAT signal transduction to promote glial cell proliferation,which affects the occurrence and recurrence of epilepsy.Astrocytes and signal transduction pathways interact with each other to play a role in the pathogenesis of epilepsy.OBJECTIVE:To investigate the effect of cannabinoid receptor type 2(CB2 R)on the activation of ERK,p38,and JNK proteins in astrocytes and MAPK pathways in juvenile rats with persistent epilepsy.METHODS:Forty healthy male Sprague-Dawley rats(18-21 days old)were randomly divided into four groups:normal control group,epilepsy model group,CB2 R agonist JWH133 group,CB2 R antagonist AM630 group.The normal control group was given only normal saline.In the other groups,rats were intraperitoneally injected with lithium chloride and pilocarpine to establish epilepsy models,and different interventions were performed.Twenty-four hours after the onset of epilepsy,brain tissues were taken.Co-expression of GFAP and p-ERK,p-p38,and p-JNK in hippocampal tissue was detected by immunofluorescence.Real-time PCR was used to detect the expression of GFAP mRNA in hippocampal tissue.RESULTS AND CONCLUSION:The co-expression of GFAP/p-ERK and GFAP/p-p38 was significantly higher in the epilepsy model group than the normal control group(P<0.05),significantly lower in the JWH133 group than the epilepsy model group(P<0.05),and significantly higher in the AM630 group than the JWH133 group(P<0.05).The co-expression of GFAP/p-JNK was significantly lower in the epilepsy model group than in normal control group(P<0.05),significantly higher in the JWH133 group than the epilepsy model group(P<0.05),and significantly lower in the AM630 group than the JWH133 group(P<0.05).The mRNA expression of GFAP was significantly decreased in the epilepsy model group compared with the normal control group(P<0.05),significantly increased in the JWH133 group compared with the epileps

关 键 词：大麻素受体2 癫痫持续状态 星形胶质细胞 通路 幼年大鼠 实验 

分 类 号：R459.9[医药卫生—治疗学] R318[医药卫生—临床医学]