抗NMDA受体脑炎相关癫痫小鼠脑组织小胶质细胞及IL-1β、TNF-α表达的变化  

Microglia and the expression levels of IL-1 and TNF-αin brain tissues of mice with anti-NMDA-receptor encephalitis-associated epilepsy

作　　者：叶霖 黄虹蜜 吴莹 杨升煜 李偲俊[1] 罗小丹[1] 马美刚[1] 吴原[1] YE Lin;HUANG Hongmi;WU Ying(Department of Traditional Chinese Medicine,the First Affiliated Hospital of Guangxi Medical University,Nanning(530021),Guangxi,China)

机构地区：[1]广西医科大学第一附属医院中医科,广西南宁530021

出　　处：《癫痫与神经电生理学杂志》2022年第3期129-134,共6页Journal of Epileptology and Electroneurophysiology(China)

基　　金：广西自然科学基金重点项目(2020GXNSFDA297012);广西医药卫生自筹经费计划课题(Z20180956)。

摘　　要：目的探讨抗NMDA受体脑炎相关癫痫小鼠海马组织的小胶质细胞及其相关炎症因子的改变。方法选取雄性C57BL/6J小鼠构建抗N-甲基-D-天冬氨酸(NMDA)受体脑炎相关癫痫小鼠模型,麻醉处死后取脑组织,应用尼氏染色观察小鼠大脑神经元细胞形态变化;ELISA检测小鼠海马组织中炎症因子IL-1β、TNF-α表达水平;蛋白印迹法检测IBA1、iNOS及Arg-1蛋白的表达水平。结果模型组小鼠中有3只死亡,死亡率为27%。尼氏染色显示模型组小鼠脑组织中部分神经元细胞变性坏死,细胞形态不完整,细胞肿胀或皱缩,轮廓模糊,界限不清。ELISA显示与对照组比较,模型组海马组织中炎症因子TNF-α、IL-1β均增高(P<0.05)。蛋白印迹法提示IBA1、iNOS显著增高(P<0.05),Arg-1和p-p38均减少(P<0.05)。结论抗NMDA受体脑炎相关癫痫可导致神经元损伤,激活M1型小胶质细胞,上调IL-1β、TNF-α表达水平。Objective To investigate the changes of microglia and related inflammatory factors in the hippocampus of mice with anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis-associated epilepsy.Methods Male C57BL/6J mice were used to establish a mouse model of anti-NMDAR encephalitis-associated epilepsy.Mouse brain tissue was collected immediately after the mice were sacrificed with anesthesia.Nissl staining was applied to observe the morphological changes of mouse brain neurons.ELISA assay was used to detect the expression levels of inflammatory factors IL-1βand TNF-αin mouse hippocampus.Western blot was performed to detect the protein expression levels of IBA1,iNOS and Arg-1.Results In model group,3 mice died and the mortality rate was 27%.Nissl staining showed that some neurons in the brain tissue of model group were degenerated and necrotic,the cell morphology incomplete illustrated by swollen or shrunken cells,blurry outlines and unclear boundaries.ELISA assays showed that when compared to control group,the inflammatory factor TNF-αand IL-1βwere increased in model group(P<0.05).Western blot results revealed that mode group had increased expression levels of IBA-1 and iNOS(P<0.05)and decreased expression levels of Arg-1 and p-p38(P<0.05)relative to control group.Conclusion Anti-NMDAR encephalitis-associated epilepsy can damage neurons,activate M1 microglia and up-regulate the expression levels of IL-1βand TNF-α.

关 键 词：N-甲基-D-天冬氨酸(NMDA) 脑炎 癫痫 小胶质细胞 炎症 

分 类 号：R512.3[医药卫生—内科学] R742.1[医药卫生—临床医学]