新医学2026，Vol.57Issue(3)：229-241,13.DOI:10.12464/j.issn.0253-9802.2025-0322
缺血性脑卒中病理进程中小胶质细胞的双重作用
Dual roles of microglia in the pathological procession of ischemic stroke:advances in molecular mechanisms and targeted therapeutic strategies
摘要
Abstract
After ischemic stroke,microglia play a"double-edged sword"role in neuroinflammation,aggravating injury while also facilitating repair.This review summarizes the dual mechanistic roles of microglia in ischemic stroke and the progress in microglia-targeted therapies.Microglial phenotypic polarization demonstrates spatiotemporal heterogeneity:in the acute phase,M1-type microglia(with high expression of CD86 and inducible nitric oxide synthase,iNOS)in the ischemic core promote inflammation,whereas in the subacute phase,M2-type microglia(with high expression of CD206 and arginase-1,Arg-1)in the penumbra facilitate tissue repair.Intermediate subtypes such as lipid droplet-rich microglia(LDRM)also exist.Mitochondrial dysfunction,enhanced glycolysis,and disordered lipid metabolism jointly drive neuroinflammation.Microglial functions are partially mediated by extracellular vesicles(EVs)released by microglia,which serve as key intercellular communication vehicles;EVs derived from different cellular sources regulate pathological progression via their bioactive cargos.Furthermore,microglia participate in the fine regulation of neurogenesis through close interactions with hippocampal neural stem cells(NSCs):the M1 phenotype inhibits regeneration,whereas the M2 phenotype supports survival and differentiation.Current microglia-targeted therapeutic strategies mainly include genetic modulation(e.g.,overexpression of sortilin-related receptor with A-type repeats;use of peroxisome proliferator-activated receptor-α agonists),engineered EV-based therapies,and metabolic interventions.However,clinical translation faces challenges such as spatiotemporal heterogeneity.Future research should focus on spatiotemporally precise interventions to facilitate the clinical application of these strategies.关键词
缺血性脑卒中/小胶质细胞/表型极化/代谢重编程/细胞外囊泡/靶向治疗Key words
Ischemic stroke/Microglia/Phenotypic polarization/Metabolic reprogramming/Extracellular vesicles/Targeted therapy引用本文复制引用
马丽,陈帅,樊泽至,郭义,林小伟..缺血性脑卒中病理进程中小胶质细胞的双重作用[J].新医学,2026,57(3):229-241,13.基金项目
国家自然科学基金(8244100603) （8244100603）
