丹参酮ⅡA对癫痫慢性期小鼠齿状回颗粒细胞病理整合的影响  

Effect of TanshinoneⅡA on abnormal integration of granule cells in the dentate gyrus of mice with chronic epilepsy

作　　者：肖新莉 秦梓通 任凯翔 郑怡秋 彭浩 强琪琦 张楚彤 杨卓远 雷琦[4] 刘建新[5] XIAO Xinli;QIN Zitong;REN Kaixiang;ZHENG Yiqiu;PENG Hao;QIANG Qiqi;ZHANG Chutong;YANG Zhuoyuan;LEI Qi;LIU Jianxin(Department of Human Anatomy,Histology and Embryology,School of Basic Medical Sciences,Xi’an Jiaotong University Health Science Center,Xi’an 710061;Clinical Medicine,Xi’an Jiaotong University Health Science Center,Xi’an 710061;Specialty of Anesthesiology,The Second Affiliated Hospital of Xi’an Medical College,Xi’an 710038;Department of Neurology,Shaanxi Provincial People’s Hospital,Xi’an 710068;Institute of Neurobiology,School of Basic Medical Sciences,Xi’an Jiaotong University Health Science Center,Xi’an 710061,China)

机构地区：[1]西安交通大学医学部基础医学院人体解剖与组织胚胎学系,陕西西安710061 [2]西安交通大学医学部,陕西西安710061 [3]西安医学院第二附属医院,陕西西安710038 [4]陕西省人民医院神经内科,陕西西安710068 [5]西安交通大学医学部神经生物研究所,陕西西安710061

出　　处：《西安交通大学学报（医学版）》2023年第4期634-643,共10页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：国家自然科学基金资助项目(No.81971210);陕西省自然科学基金(No.2022JM-486,No.2022JM-590);国家大学生创新训练项目(No.GJ202110698186)。

摘　　要：目的拟通过使用颞叶癫痫(temporal lobe epilepsy,TLE)小鼠模型,经丹参酮ⅡA(TanⅡA)干预后,阐明其对齿状回颗粒细胞病理整合的作用及其分子机制。方法使用匹罗卡品诱导小鼠癫痫持续发作(SE),TanⅡA 5 mg/kg进行干预,SE 2个月后,利用Morris水迷宫检测学习记忆能力,视频监测自发性癫痫发作,取海马进行Timm、prox-1、DCX、SynⅠ染色,并采用Western blotting检测PTEN、p-AKT、p-S6蛋白表达。结果TanⅡA降低了慢性期TLE小鼠齿状回Timm评分、SynⅠ、PSD-95、p-AKT、pS6的表达及上调了PTEN的表达,减少了颗粒细胞苔藓纤维芽发及底树突的形成,视频监测结果显示TanⅡA降低了自发癫痫Racine评分5级的发作频率。结论TanⅡA可能通过调控PTEN/AKT/mTOR通路从而有效抑制颗粒细胞苔藓纤维芽发和底树突的发生,进而改善TLE小鼠慢性期癫痫的齿状回病理结构的形成与发展,从而起到抗癫痫的作用。Objective To clarify the role and molecular mechanism of TanshinoneⅡA(TanⅡA)in the pathological integration of granule cells in the dentate gyrus(DG)by using the mouse model of temporal lobe epilepsy(TLE).Methods Status epilepticus(SE)was induced in the mice with pilocarpine and treated with TanⅡA 5 mg/kg.After two months,Morris water maze was used to examine the spatial learning and memory ability and video surveillance was used to monitor spontaneous seizures.The DG was removed for staining of Timm,Prox-1,DCX and SynⅠ.PTEN,p-AKT,and p-S6 expressions were observed by Western blotting.Results TanⅡA decreased Timm score,SynⅠ,PSD-95 and pS6 levels,and increased the level of PTEN in the DG,and attenuated the formation of mossy fiber sproutings and basal dendrites of the granule cells.Video surveillance showed that TanⅡA reduced the frequency of Racine’grade 5 seizures.Conclusion TanⅡA can effectively attenuate the abnormal integration of the granule cells in the DG by regulating PTEN/AKT/mTOR pathway and thus plays an anti-epileptic role.

关 键 词：颞叶癫痫 丹参酮ⅡA 齿状回 mTOR通路 

分 类 号：R322.8[医药卫生—人体解剖和组织胚胎学]