中药调控小胶质细胞极化平衡治疗神经退行性疾病的机制研究进展  

Mechanism of Traditional Chinese Medicine in Treatment of Neurodegenerative Diseases by Regulating Polarization Balance of Microglia:A Review

作　　者：赵浩林 孙世标 秦国燕 丁艳怡 赵铎[2] ZHAO Haolin;SUN Shibiao;QIN Guoyan;DING Yanyi;ZHAO Duo(Henan University of Chinese Medicine,Zhengzhou 450000,China;The First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450000,China)

机构地区：[1]河南中医药大学,郑州450000 [2]河南中医药大学第一附属医院,郑州450000

出　　处：《中国实验方剂学杂志》2024年第2期244-253,共10页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家重点研发计划“中医药现代化”项目(2018YFC1704103);国家中医药管理局全国名老中医药专家传承工作室建设项目(国中医药人教函[2012]149号);河南省中医药科学研究专项(2019ZYBJ09)。

摘　　要：神经炎症是神经退行性疾病(NDs)的共同病理特征,而小胶质细胞(MG)是具有独特发育起源的脑内常驻巨噬细胞,是神经炎症的核心驱动因素,可通过不同极化状态参与NDs的发生、发展过程,且在调节神经发生、突触塑造和维持体内平衡等方面发挥着关键作用。MG根据功能可分为M1促炎表型和M2抗炎表型,其中M1表型释放的炎症介质可导致神经变性和髓鞘损伤,而抑制炎症反应、促进组织修复则需要M2表型的激活。中药在多途径、多靶点及双向调节的优势下,可调控MG的极化平衡,且在阿尔茨海默病、帕金森病、多发性硬化等NDs中具有双重作用。中药活性成分及其复方可通过调控磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)、NOD样受体蛋白3(NLRP3)、信号转导及转录激活因子1(STAT1)、核转录因子-κB(NF-κB)等通路抑制MG的活化,促进M1型向M2型极化,减少白细胞介素(IL)-6、肿瘤坏死因子-α(TNF-α)等促炎因子的表达,增加IL-10、精氨酸酶-1(Arg-1)等抗炎因子的分泌,降低阿尔茨海默病中β-淀粉样蛋白沉积和Tau样蛋白表达、减轻帕金森病中多巴胺能神经元损伤、缓解多发性硬化的脱髓鞘、炎性细胞浸润及相关临床症状。中药双向调控MG M1/M2极化平衡是治疗NDs的潜在策略,而该文重点探讨中药单体及其复方调控MG极化平衡治疗NDs的作用靶点,旨在进一步研究和归纳现有的研究成果,从而为将来治疗NDs提供思路和依据。Neuroinflammation is a common pathological feature of neurodegenerative diseases(NDs).Microglia(MG),a resident macrophage in the brain with a unique developmental origin,is the core driver of neuroinflammation.It can participate in the occurrence and development of NDs through different polarization states and play a key role in regulating neurogenesis and synapse shaping and maintaining homeostasis.MG can be divided into M1 pro-inflammatory phenotype and M2 anti-inflammatory phenotype according to its function.The inflammatory mediators released by the M1 phenotype can lead to nerve degeneration and myelin sheath damage,while the activation of the M2 phenotype is required to inhibit the inflammatory response and promote tissue repair.With the advantages of multi-pathway,multi-target,and bidirectional regulation,traditional Chinese medicine can regulate the polarization balance of MG and has dual effects on NDs such as Alzheimer's disease,Parkinson's disease,and multiple sclerosis.The active components of traditional Chinese medicine and its compound can inhibit the activation of MG by regulating phosphatidylinositol-3-kinases/protein kinase B(PI3K/Akt),NOD-like receptor thermal protein domain associated protein 3(NLRP3),signal transducer and activator of transcription factor1(STAT1),nuclear transcription factor kappa B(NF-κB),and other pathways,promote the polarization of M1 phenotype to M2 phenotype,reduce the expression of interleukin(IL)-6,tumor necrosis factor-α(TNF-α),and other pro-inflammatory factors,and increase the secretion of IL-10,arginase-1(Arg-1),and other anti-inflammatory factors.It can also reduceβ-amyloid deposition and tau protein expression in Alzheimer's disease,alleviate dopaminergic neuronal damage in Parkinson's disease,and relieve demyelination,inflammatory cell infiltration,and related clinical symptoms of multiple sclerosis.The bidirectional regulation of the M1/M2 polarization balance of MG by traditional Chinese medicine is a potential strategy for the treatment of NDs.This paper

关 键 词：神经退行性疾病 小胶质细胞极化 中药 信号通路 机制 

分 类 号：R2-0[医药卫生—中医学] R22R285.5R2-031R856.2