脊髓损伤中的小胶质细胞:M1/M2表型极化发挥神经毒性/神经保护作用  

Microglia in spinal cord injury:M1/M2 phenotypic polarization and neurotoxic/neuroprotective effects

作　　者：李传鸿 俞兴[1] 杨永栋[1] 赵赫[1] Li Chuanhong;Yu Xing;Yang Yongdong;Zhao He(Department of Orthopedics,Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China)

机构地区：[1]北京中医药大学东直门医院骨科,北京市100700

出　　处：《中国组织工程研究》2022年第14期2265-2272,共8页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金面上项目(81973882),项目负责人:俞兴;国家自然科学基金青年科学基金项目(81804119),项目负责人:杨永栋;北京中医药大学东直门医院2020科技创新专项(DZMKJCX-2020-049),项目负责人:俞兴。

摘　　要：背景:大量研究发现,小胶质细胞在脊髓损伤后被激活,发挥着神经保护和神经毒性的双向作用,与继发性损伤密切相关。目的:对脊髓损伤后M1/M2表型小胶质细胞的特征、以M1/M2表型为靶点的脊髓损伤干预研究进展及针对脊髓损伤后小胶质细胞未来可能的研究方向等内容进行综述。方法:第一作者在2021年5月以"microglia,spinal cord injury,M1 phenotype,M2 phenotype,polarization,activation,activated,regulation"为检索词在PubMed数据库中检索相关文献,在阅读文题及摘要后根据入选与排除标准筛选检索到的文章,最后共纳入文献76篇进行归纳总结与综述。结果与结论:(1)小胶质细胞独特的细胞起源与发育环境赋予它特殊的生物学功能,生理状态下的小胶质细胞依靠高度活跃的分枝状突起持续监测脊髓组织内微环境变化,发挥免疫监视功能。(2)脊髓损伤发生后,小胶质细胞快速响应微环境异常信号,极化为M1和M2表型,分别发挥神经毒性与神经保护作用。(3)大量基础实验证实,中药提取物、现代临床药物、基因表达调控、细胞移植、生物材料等干预措施可调控小胶质细胞的M1/M2表型,改善啮齿动物脊髓损伤模型的预后。但目前对于M1/M2型小胶质细胞的数量及比例的最佳调控目标尚无统一结论,同时缺乏靶向作用于小胶质细胞的活体给药方式,未来应深入探究促进M1/M2型小胶质细胞功能平衡的方法,将脊髓损伤后的炎症反应限定在有利于损伤脊髓修复的水平上,随着对脊髓损伤后小胶质细胞极化表型精准调控机制的深入研究,相应的基础研究成果有望用于临床治疗。BACKGROUND:A large number of studies have shown that microglia are activated after spinal cord injury,which play a dual role of neuroprotection and neurotoxicity,and are closely related to secondary spinal cord injury.OBJECTIVE:To review the characteristics of microglia’M1/M2 phenotype after spinal cord injury,the progress in spinal cord injury intervention studies targeting M1/M2 phenotype and the possible research directions of microglia after spinal cord injury.METHODS:In May 2021,the first author searched PubMed database with the keywords of“microglia,spinal cord injury,M1 phenotype,M2 phenotype,polarization,activation,activated,regulation.”After reading the title and abstract,the retrieved articles were screened according to the inclusion and exclusion criteria.Finally,a total of 76 included literatures were summarized and reviewed.RESULTS AND CONCLUSION:Microglia have special biological functions due to its unique cell origin and development environment.In physiological state,microglia rely on its highly active branching process to continuously monitor the changes of microenvironment in the spinal cord tissue and play the function of immune surveillance.After spinal cord injury,microglia rapidly respond to abnormal microenvironmental signals and are polarized into M1 and M2 phenotypes,exerting neurotoxic and neuroprotective effects,respectively.A large number of basic experiments have demonstrated that interventions such as Chinese herbal extracts,clinical drugs,regulation of gene expression,cell transplantation,biomaterials can regulate the M1/M2 phenotype of microglia and improve the prognosis of spinal cord injury in a rodent model.However,no consensus has been reached on the optimal regulation target for the quantity and proportion of M1 and M2 phenotypes,and in vivo drug delivery targeting microglia is lacking.Future explorations should focus on promoting the functional balance between M1 and M2 phenotypes to limit the level of inflammatory response after spinal cord injury,which is conducive to

关 键 词：脊髓损伤 继发性损伤 小胶质细胞 M1表型 M2表型 炎症反应 神经保护 综述 

分 类 号：R459.9[医药卫生—治疗学] R364[医药卫生—临床医学]