国际神经病学神经外科学杂志2024，Vol.51Issue(4)：28-35,8.DOI:10.16636/j.cnki.jinn.1673-2642.2024.04.005
炎症小体激活小胶质细胞促进异常新生神经元形成在锂-毛果芸香碱致痫大鼠中的作用机制
Mechanism of action of inflammasome in promoting the formation of abnormal neonatal neurons by activating microglial cells in rats with lithium-pilocarpine-induced epilepsy
摘要
Abstract
Objective To investigate the activation of inflammasome and microglial cells and the formation of abnormal neonatal neurons in a rat model of lithium-pilocarpine-induced epilepsy,as well as the mechanism of action of inflammasome in the development and progression of epilepsy by activating microglial cells and promoting the formation of abnormal neonatal neurons.Methods Rats were given intraperitoneal injection of lithium and pilocarpine to establish a model of epilepsy.Rats were divided into Sham group(saline control group,n=12),Pilo group(lithium-pilocarpine epileptogenic group,n=20)and Pilo+MCC950 group(lithium-pilocarpine epileptogenic followed by administration of NLRP3 inhibitor group,n=20).The behavioral manifestations of epilepsy were observed in the acute stage;pathological sections were used to observe brain tissue injury and cell activation;molecular assays were used to measure the expression of inflammasome and other molecules;in vitro cell model rescue experiments were used to verify the effect of inflammasome.Results In the Pilo group,there were six rats with grade V seizures,five with grade Ⅳ seizures,and two with grade Ⅲseizures,while in the Pilo+MCC950 group,there were no rats with grade V seizures,and there were six rats with grade Ⅳseizures,eight with grade Ⅲ seizures,and two with grade Ⅱ seizures.Compared with the Pilo+MCC950 group,the Pilo group had a significantly shorter latency period of myotonic seizures and significantly higher number and longer duration of grade ≥Ⅲ seizure.The Pilo group had significantly higher levels of NLRP3,pro-caspase-1,four inflammatory cytokines,BNDF,and ERK than the Pilo+MCC950 group.Immunofluorescence assay showed the activation of a large number of microglial cells and the presence of a large number of abnormal neonatal neurons in the Pilo group.After in vitro cell experiments,the results of ELISA validated the role of inflammasome.Conclusion In the rat model of lithium-pilocarpine-induced epilepsy,inflammasome NLRP3 is activated by external inflammatory stimuli and then produces a large number of inflammatory cytokines,thereby activating microglial cells to secrete BDNF and activate the ERK signaling pathway,and thus it regulates the formation and aggregation of abnormal neonatal neurons and participates in the development and progression of epilepsy.关键词
癫痫/炎症小体/炎症因子/小胶质细胞/新生神经元Key words
epilepsy/inflammasome/inflammatory cytokines/microglial cells/neonatal neurons分类
医药卫生引用本文复制引用
周乐超,刘远静,陈良雄,苏晓玲,廖小红,张治平..炎症小体激活小胶质细胞促进异常新生神经元形成在锂-毛果芸香碱致痫大鼠中的作用机制[J].国际神经病学神经外科学杂志,2024,51(4):28-35,8.基金项目
湖南省卫生健康委科研计划项目(202203073346). （202203073346）
