Notch1蛋白调控的小胶质细胞极化对小鼠癫痫发作的保护作用  

Protective effect of Notch1-regulated microglial polarization against epileptic seizure in mice

作　　者：朱洋洋 刘梦[1] 杨道迪 胡依依 方敬献[1] ZHU Yangyang;LIU Meng;YANG Daodi;HU Yiyi;FANG Jingxian(Department of Neurology,Nanyang First People’s Hospital,Nanyang 473000,China;Department of Pathophysiology,School of Basic Medicine,School of Medicine of Zhengzhou University,Zhengzhou 450001,China)

机构地区：[1]南阳市第一人民医院神经内科,河南南阳473000 [2]郑州大学医学院基础医学院病理生理学教研室,郑州450001

出　　处：《中国医科大学学报》2025年第3期228-232,共5页Journal of China Medical University

基　　金：河南省科技发展计划(222102310145)。

摘　　要：目的探讨Notch1蛋白调控的小胶质细胞极化对小鼠癫痫发作的保护作用。方法采用Notch1正常表达(Notch1^(normal))和Notch1高表达(Notch1^(over))小鼠构建戊四唑(PTZ)点燃癫痫模型,以Racine等级达到Ⅳ级为标准,评价Notch1表达对癫痫发作的影响。通过免疫荧光染色检测小鼠颞叶组织中小胶质细胞活化和极化,采用酶联免疫吸附试验检测小鼠颞叶组织中炎性细胞因子水平。结果Notch1高表达对癫痫发作有较强的抵抗作用。与Notch1^(normal)+Sal组相比,Notch1^(normal)+PTZ组小鼠颞叶组织中Iba1、CD16和Arg1蛋白相对荧光强度明显增加(P<0.05),TNF-α、IL-6、IL-10含量明显增加(P<0.05);与Notch1^(normal)+PTZ组相比,Notch1^(over)+PTZ组小鼠颞叶组织Iba1和CD16蛋白相对荧光强度明显降低(P<0.05),Arg1蛋白相对荧光强度明显增加(P<0.05),TNF-α、IL-6含量明显减少(P<0.05),IL-10含量进一步增加(P<0.05)。结论Notch1蛋白高表达能够明显提高M2型小胶质细胞极化,抑制M1型小胶质细胞极化,增强小鼠对癫痫发作的抵抗性。Objective To investigate the protective effect of Notch1-regulated microglial polarization against epileptic seizure in mice.Methods The pentylenetetrazole(PTZ)kindling models of epilepsy were established in mice with normal(Notch1^(normal))and high(Notch1^(over))expression of the Notch1 protein,with Racine gradeⅣset as the standard,to evaluate the effect of Notch1 expression on seizure susceptibility.Microglial activation and polarization in the temporal lobe tissues of mice were detected using immunofluorescence staining,and the levels of inflammatory cytokines in the temporal lobe tissues was detected using an enzyme-linked immunosorbent assay.Results High Notch1 expression showed high resistance to seizures.Compared with the Notch1^(normal)+Sal group,the relative fluorescence intensity of Iba1,CD16,and Arg1 proteins in the temporal lobes of mice in the Notch1^(normal)+PTZ group,as well as the TNF-α,IL-6,and IL-10 levels significantly increased(P<0.05).Compared with the Notch1^(normal)+PTZ group,the relative fluorescence intensity of Iba1 and CD16 proteins in the temporal lobes of mice in the Notch1^(over)+PTZ group significantly decreased(P<0.05),the relative fluorescence intensity of Arg1 protein significantly increased(P<0.05),the TNF-αand IL-6 levels significantly decreased(P<0.05),and the IL-10 level further increased(P<0.05).Conclusion High Notch1 protein expression significantly enhanced M2-type microglial polarization,inhibited M1-type microglial polarization,and increased resistance to seizure susceptibility in mice.

关 键 词：NOTCH1 小胶质细胞 极化 炎症反应 癫痫 

分 类 号：R742.1[医药卫生—神经病学与精神病学]