TRPV4在海人藻酸介导的小鼠癫痫模型中的作用  

Role of Transient receptor potential vanilloid 4 in the kainic acid experimental model of epilepsy

作　　者：司沛沛[1] 毛卓峰[1] 曲珍珍[1] 王维平[1] 谢涛[1] 甄军丽[1] 张文琳[1] 吴建坤[1] 崔华伟 贾丽景[1] Si Peipei;Mao Zhuofeng;Qu Zhenzhen;Wang Weiping;Xie Tao;Zhen Junli;Zhang Wenlin;Wu Jiankun;Cui Huawei;Jia Lijing(Department of Neurology,the Second Hospital of Hebei Medical University,Shijiazhuang 050000,China)

机构地区：[1]河北医科大学第二医院神经内科,石家庄050000

出　　处：《脑与神经疾病杂志》2023年第9期570-576,共7页Journal of Brain and Nervous Diseases

基　　金：河北省卫生健康委青年科技课题(20180326)。

摘　　要：目的探讨瞬时感受器电位辣椒素受体4型(TRPV4)在小鼠癫痫持续状态(SE)中的作用及其可能的机制。方法本实验利用腹腔注射海人藻酸(KA)建立小鼠SE模型,随机分为Control组、KA组、HC-0670475 mg·kg^(-1)组、HC-06704710 mg·kg^(-1)组、HC-06704720 mg·kg^(-1)组及Vehicle组;依据Racine行为分级法记录小鼠癫痫发作程度,同时记录小鼠达到SE的潜伏期、各组小鼠SE发生率及小鼠存活率;利用Western-blot和Real-Time PCR检测海马组织中TRPV4表达水平;应用ELISA试剂盒检测海马组织中MDA、SOD和GSH含量。结果观察到SE后6 h小鼠海马区TRPV4的表达水平升高(P<0.05),在24 h达到高峰;预先应用TRPV4拮抗剂HC-067047延长了诱发小鼠SE的潜伏期(P<0.05),减少SE的发病率(P<0.05),增加小鼠的存活率(P<0.05);此外,证实了SE可以引起海马区MDA含量增加,SOD、GSH活性降低(<0.05),而HC-067047预处理可以降低MDA含量,增加SOD、GSH活性(P<0.05)。结果TRPV4可能通过增加海马区氧化应激损伤参与小鼠癫痫持续状态。Objective To investigate the role of transient receptor potential vanilloid 4(TRPV4)in status epilepticus(SE)in mice and its possible mechanism.Methods Mice were injected with Kainic acid(KA)intraperitoneally to establish SE model.They were randomly divided into Control group,KA group,HC-0670475 mg·kg^(-1)group,HC-06704710 mg·kg^(-1)group,HC-06704720 mg·kg^(-1)group and vehicle group.The observers recorded the severity of seizures using racine behavior grading method.Meanwhile,the latency period of SE,the incidence of SE and the survival rate of mice in each group were recorded.The expression of TRPV4 in hippocampus was detected by Western-blot and Real-Time PCR.Results The expression level of TRPV4 in hippocampus of mice increased at 6 h after SE(P<0.05)and reached its peak at 24 h.Pretreatment with TRPV4 antagonist HC-067047 prolonged the latency of SE(P<0.05),decreased the incidence of SE(P<0.05),increased the survival rate of mice(P<O.05).In addition,it was confirmed that SE can increase the content of MDA in hippocampus and decrease the activities of SOD and CSH(P<0.05),pretreatment with HC-067047could decrease MDA content and increase SOD and GSH activities(P<0.05).Conclusion TRPV4 may be involved in status epilepticus by increasing oxidative stress damage in hippocampus of mice.

关 键 词：TRPV4 癫痫 氧化应激 海人藻酸 海马 

分 类 号：R742.1[医药卫生—神经病学与精神病学]