NLRP3在TRPC3介导癫痫的过程中表达升高  

Upregulation of NLRP3 in the Process of TRPC3 Facilitating Epilepsy

作　　者：卢敏[1] 杨虹[1] 贺细菊[2] Lu Min;Yang Hong;He Xiju(Department of Histology and Embryology,Hubei University of Medicine,Shiyan 442000,China;Department of Human Anatomy,Hubei University of Medicine,Shiyan 442000,China)

机构地区：[1]湖北医药学院组织胚胎学教研室,十堰442000 [2]湖北医药学院解剖学教研室,十堰442000

出　　处：《华中科技大学学报（医学版）》2019年第6期650-654,共5页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：湖北省教育厅科学研究计划指导性项目(No.B2019104);湖北医药学院人才启动金资助计划项目(No.2018QDJZR10)

摘　　要：目的研究经典型瞬时受体电位通道蛋白3(transient receptor potential canonical 3,TRPC3)在促发癫痫过程中对焦亡相关因子NLRP3表达的影响,探讨TRPC3在癫痫发病过程中的作用机制。方法 HEK293细胞系转染TRPC3,采用钙影像技术检测TRPC3介导钙离子内流的作用;采用免疫组织化学法检测癫痫患者手术切除海马标本中NLRP3的表达情况;制作海人酸(KA)癫痫大鼠模型,利用TRPC3特异性抑制剂Pyr3阻断TRPC3,观察动物行为学改变,以免疫组织化学法和Western blot技术检测动物海马组织中NLRP3的表达水平。结果 TRPC3可通过ROCE和SOCE途径介导钙离子内流进入细胞;癫痫患者和癫痫模型大鼠海马组织内NLRP3水平显著升高;阻断TRPC3后模型大鼠癫痫发作减轻,且NLRP3表达水平降低。结论 TRPC3促进癫痫发病的过程与激活炎性体NLRP3有关。Objective To study the effects of transient receptor potential canonical 3(TRPC3)on the pyroptosis relating factor-NLRP3 during the process of epilepsy,and to explore the mechanism of TRPC3 in the pathogenesis of epilepsy.MethodsHEK293 cells were transfected with TRPC3,and then Calcium image was used to detect the function of TRPC3 in mediating Ca2+.Immunohistochemistry was used to detect the NLRP3 level in hippocampal specimens from epilepsy patients receiving hippocampal resection.Using Pyr3(a specific inhibitor of TRPC3)to block TRPC3 before KA-induced epilepsy in SD rats,then animal behavior was observed,and immunohistochemistry and Western blotting were used to detect the expression level of NLRP3 in hippocampal tissues of rats.Results TRPC3 mediated Ca2+ entry in both ROCE and SOCE ways.The level of NLRP3 was significantly increased in hippocampus of epilepsy patients and model animals.Blocking TRPC3 alleviated seizures and simultaneously reduced NLRP3 level.ConclusionThe process of TRPC3 facilitating epilespy is related to activation of NLRP3 inflammasome.

关 键 词：经典型瞬时受体电位通道蛋白3 癫痫 焦亡 炎性体 NLRP3 

分 类 号：R742.1[医药卫生—神经病学与精神病学]