神经药理学报 ›› 2022, Vol. 12 ›› Issue (1): 57-64.DOI: 10.3969/j.issn.2095-1396.2022.01.009

• 综述 • 上一篇    

不同状态下的小胶质细胞对脑缺血发病机制的作用

刘子铭,郭宝,张丹参,景永帅   

  1. 河北科技大学化学与制药工程学院,石家庄,050018,中国
  • 出版日期:2022-02-26 发布日期:2023-08-30
  • 通讯作者: 张丹参,博士生导师;研究方向:神经药理学;Tel:+86 - 0311 - 81668016,E - mail:zhangds2011@126.com
  • 作者简介:刘子铭,硕士研究生;研究方向:药理学;E - mail:1014922441@qq.com
  • 基金资助:
    河北省重点研发计划项目生物医药专项项目(No.20372509D),河北省自然科学基金项目(No.H2020208032)

Role of Microglia in Different States on the Pathogenesis of Cerebral Ischemia

LIU Zi - ming,GUO Bao,ZHANG Dan - shen,JING Yong - shuai   

  1. College of Chemical and Pharmaceutical Engineering,Hebei University of Science and Technology,Shijiazhuang, 050018,China
  • Online:2022-02-26 Published:2023-08-30

摘要:

小胶质细胞作为中枢神经系统中最主要的免疫细胞,在缺血性损伤中涉及的炎症反应以及神经修复过 程中起着重要的作用。生理情况下,小胶质细胞分泌营养因子对神经元提供营养支持,并参与神经环路的建立。 脑缺血损伤时,小胶质细胞上的Toll 样受体能识别并吞噬坏死的神经元,清除凋亡神经元;同时小胶质细胞也会释 放出有害的细胞因子,加重神经元的损伤。脑缺血损伤发生时小胶质细胞会活化成两种状态:一种是促炎表型(M1 型):分泌白细胞介素-1(interleukin-1,IL-1),IL - 6 和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α),加重炎症 反应;一种是抗炎表型(M2 型):分泌IL - 4,IL - 10 和TGF - β1,抑制炎症促进组织修复。脑缺血发生后,与小胶质细 胞相关的通路例如NF - κB 通路、TLR\NF - κB 通路、NLRP3 炎性小体通路、Notch 信号通路、p38MAPK 信号通路等 可能会被激活,因此药物通过不同的作用机制或者通路对小胶质细胞的活化产生影响,可能是一种新的治疗策略。

关键词: 小胶质细胞, 脑缺血, 炎性因子, 通路

Abstract:

As the most important immune cell in the central nervous system,microglia play an important role in the inflammatory response involved in ischemic injury and in the process of nerve repair. Under physiological conditions,microglia secrete nutritional factors to provide nutritional support to neurons and participate in the establishment of neural circuits. In cerebral ischemic injury,toll - like receptors on microglia can recognize and engulf necrotic neurons and clear apoptotic neurons;At the same time,microglia also release harmful cytokines, aggravating neuronal damage. When cerebral ischemic injury occurs,microglia are activated into two states,one is the pro - inflammatory phenotype (M1 type):secretion of IL - 1,IL - 6 and TNF -α ,aggravating the inflammatory response;One is the anti - inflammatory phenotype( M2 type):secretes IL - 4,IL - 10 and TGF - β1,inhibits inflammation and promotes tissue repair. After cerebral ischemia,microglia - related pathways such as NF -κ B pathway,TLR\NF -κ B pathway, NLRP3 inflammasome pathway,Notch signaling pathway,p38MAPK signaling pathway etc,may be activated. Therefore,drugs affect the activation of microglia through different mechanisms of action or pathways,which may be a new therapeutic strategy.

Key words: microglia, cerebral ischemia, inflammatory factor, pathway