TLR4/NF-κB信号通路在小胶质细胞介导的脑缺血神经炎症中的作用及中药干预研究进展

The role of TLR4/NF-κB signaling pathway in microglia-mediated cerebral ischemic neuroinflammation and advances in traditional Chinese medicine intervention

关键词:  缺血性脑卒中  神经炎症反应  小胶质细胞  TLR4/NF-κB信号通路  中药治疗

Key words:  ischemic stroke  neuroinflammation  microglia  TLR4/NF-κB signaling pathway  traditional Chinese medicine treatment

摘要:

缺血性脑卒中是一种具有极高发病率、致死率和致残率的脑血管疾病，严重影响人们的健康和生活质量。研究表明，缺血性脑卒中后的神经炎症会显著加重脑组织损伤，小胶质细胞扮演关键角色。大脑发生炎症、感染或创伤时，小胶质细胞迅速激活并具备吞噬功能。激活后的小胶质细胞双向分化为具有神经毒性的M1型或具有神经保护作用的M2型，促进小胶质细胞向M2型极化具有明显的抗炎效应。小胶质细胞表面广泛表达Toll样受体（TLRs）家族中的TLR4，其通过激活炎症蛋白核转录因子-κB（NF-κB）下游信号通路调节神经炎症进程。中医药具有多靶点、多通路、多成分及不良反应小、安全性高的特点。研究表明，中药通过多种途径调控小胶质细胞的增殖与活化，抑制其介导的神经炎症反应，同时减轻氧化应激反应、抗细胞凋亡、调节细胞自噬及保护血脑屏障以抵抗脑缺血损伤。因此，文章通过阐述Toll样受体4（TLR4）/NF-κB信号通路在小胶质细胞极化中的作用机制，并总结中药治疗缺血性脑卒中的最新研究成果，以期为新药研发及提升中药在临床应用中的有效性提供参考依据。

Abstract:

Ischemic stroke is a cerebrovascular disease with high morbidity,mortality,and disability rates,seriously affecting people's health and quality of life. Studies have shown that neuroinflammation after ischemic stroke significantly aggravates brain tissue damage,in which microglia play a key role. Upon brain inflammation,infection,or trauma,microglia are rapidly activated and acquire phagocytic function. The activated microglia polarize into either neurotoxic M1 or neuroprotective M2 phenotypes. Promoting microglial polarization toward the M2 phenotype demonstrates significant anti-inflammatory effects. Toll-like receptor 4(TLR4),a member of the TLR family,is widely expressed on microglia and regulates neuroinflammation by activating the downstream nuclear factor-κB(NF-κB) signaling pathway. Traditional Chinese medicine(TCM) is characterized by multi-target,multi-pathway,and multi-component actions,along with minimal side effects and high safety. Research indicates that TCM modulates microglial proliferation and activation through various mechanisms,suppresses microglia-mediated neuroinflammation, and alleviates oxidative stress,apoptosis,and autophagy dysregulation while protecting the blood-brain barrier against cerebral ischemic injury. Therefore,this article elucidates the mechanism of the TLR4/NF-κB signaling pathway in microglial polarization and summarizes recent advances in TCM for ischemic stroke treatment,aiming to provide references for novel drug development and enhance the clinical efficacy of TCM.