多发性硬化中TLRs/MyD88/NF-κB信号通路的作用及机制  

The role and mechanism of TLRs/MyD88/NF-κB signaling pathway in multiple sclerosis

作　　者：陈莹 夏天晴 滑键林 殷金珠 宋丽娟 王青 尉杰忠[3] 黄建军 马存根[1] Chen Ying;Xia Tianqin;Hua Jianlin;Yin Jinzhu;Song Lijuan;Wang Qing;Yu Jiezhong;Huang Jianjun;Ma Cungen(The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine/Research Center of Neurobiology,Shanxi University of Chinese Medicine,Jinzhong 030619,Shanxi Province,China;Department of Neurosurgery,General Hospital of Sinopharm Coal Group,Datong 037003,Shanxi Province,China;Institute of Brain Science,Shanxi Datong University,Datong 037009,Shanxi Province,China)

机构地区：[1]山西中医药大学神经生物学研究中心/国家中医药管理局多发性硬化益气活血重点研究室,山西省晋中市030619 [2]国药同煤集团总医院神经外科,山西省大同市037003 [3]山西大同大学脑科学研究所,山西省大同市037009

出　　处：《中国组织工程研究》2024年第28期4578-4585,共8页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金面上项目(81473577),项目负责人:马存根;国家自然科学基金面上项目(81903596),项目负责人:王青;2022年山西省科技创新青年人才团队(202204051001028),项目负责人:宋丽娟;山西省应用基础研究计划项目(201901D211538),项目负责人:宋丽娟;山西省卫健委医学科技领军团队(2020TD05),项目负责人:马存根;山西中医药大学学科建设经费(2023XKJS-02),项目负责人:马存根;山西中医药大学2022年度科技创新团队(2022TD2006),项目负责人:王青;山西中医药大学2022年度科技创新团队(2022TD2010),项目负责人:宋丽娟;山西中医药大学青年科学家培育项目(2021-PY-QN-09),项目负责人:宋丽娟。

摘　　要：背景:多发性硬化是以T细胞介导的中枢神经系统慢性炎性脱髓鞘疾病,Toll样受体(Toll-like receptors,TLRs)/髓样分化因子88(myeloid differentiation factor 88,MyD88)/核转录因子κB(nuclear factor kappa-B,NF-κB)信号通路在疾病发生发展过程中有重要作用,探究出信号通路的具体作用机制对进一步治疗该疾病,改善患者的预后至关重要。目的:综述TLRs/MyD88/NF-κB信号通路及其在多发性硬化/实验性自身免疫性脑脊髓炎模型中的作用,并就抑制该信号通路为多发性硬化的治疗提供新的思路和策略。方法:检索中国知网、万方及PubMed数据库在2002年1月至2022年12月与文章主题相关的文献,最终纳入61篇文献进行分析。结果与结论:①TLRs/MyD88/NF-κB信号通路是介导炎性免疫反应的重要信号通路;②TLRs/MyD88/NF-κB信号通路通过调节树突状细胞的抗原提呈、破坏血脑屏障的完整性、促进T细胞、B细胞和小胶质细胞的激活等途径,在多发性硬化的发展中发挥了重要的作用;③通过靶向作用于TLRs、MyD88和NF-κB分子,抑制TLRs、MyD88和NF-κB的激活或信号传导,减少促炎因子的分泌可以达到治疗多发性硬化的目的;④动物实验研究表明,中药的活性成分如黄酮类和苷类、中药复方如补阳还五汤也可通过影响TLRs/MyD88/NF-κB信号通路治疗实验性自身免疫性脑脊髓炎,这为寻找靶向TLRs/MyD88/NF-κB信号通路治疗多发性硬化的药物指明方向。BACKGROUND:Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system mediated by T cells.The Toll-like receptors(TLRs)/myeloid differentiation factor 88(MyD88)/nuclear factor kappa-B(NF-κB)signaling pathway plays an important role in the development of the disease.Exploring the specific mechanism of the signaling pathway is essential for further treatment of the disease and improving the prognosis of patients.OBJECTIVE:To review the TLRs/MyD88/NF-κB signaling pathway and its role in multiple sclerosis/experimental autoimmune encephalomyelitis models,which provides new ideas and strategies for the treatment of multiple sclerosis by inhibiting the TLRs/MyD88/NF-κB signaling pathway.METHODS:The literature related to the topic from January 2002 to December 2022 was searched in CNKI,WanFang and PubMed databases.A total of 61 articles were finally included for analysis.RESULTS AND CONCLUSION:The TLRs/MyD88/NF-κB signaling pathway is an important pathway that triggers a pro-inflammatory immune response.The TLRs/MyD88/NF-κB signaling pathway plays an important role in the development of multiple sclerosis by regulating the antigen presentation of dendritic cells,destroying the integrity of the blood-brain barrier,and promoting the activation of T cells,B cells and microglia.By targeting TLRs,MyD88 and NF-κB molecules,inhibiting the activation or signal transduction of TLRs,MyD88 and NF-κB,and reducing the secretion of pro-inflammatory factors,multiple sclerosis can be treated.Animal studies have shown that active ingredients of traditional Chinese medicines,such as flavonoids and glycosides,and traditional Chinese medicine compound formulas,such as Buyang Huanwu Tang,can also treat experimental autoimmune encephalomyelitis by regulating the TLRs/MyD88/NF-κB signaling pathway,which points to the direction of searching for medicines targeting the TLRs/MyD88/NF-κB signaling pathway for the treatment of multiple sclerosis.

关 键 词：多发性硬化 TLRS MYD88 NF-ΚB 小胶质细胞 炎症反应 机制 治疗 

分 类 号：R459.9[医药卫生—治疗学] R363[医药卫生—临床医学] R364