MAPK信号通路在防治类风湿关节炎中的作用及中药干预研究进展  

Role of MAPK Signaling Pathway in Prevention and Treatment of Rheumatoid Arthritis and Chinese Medicine Intervention:A Review

作　　者：李辉明 薄双娟 邢涛[1] 魏国俊[1] 王志勇[1] 田雪梅[1] 李盛华[1] 刘涛 李育光 魏晓涛 LI Huiming;BO Shuangjuan;XING Tao;WEI Guojun;WANG Zhiyong;TIAN Xuemei;LI Shenghua;LIU Tao;LI Yuguang;WEI Xiaotao(Gansu Provincial Hospital of Traditional Chinese Medicine,Lanzhou 730050,China;Gansu University of Chinese Medicine,Lanzhou 730050,China)

机构地区：[1]甘肃省中医院,兰州730050 [2]甘肃中医药大学,兰州730050

出　　处：《中国实验方剂学杂志》2024年第14期288-298,共11页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81660802);甘肃省自然科学基金项目(22JR5RA628,23JRRA1679);甘肃省中医药科研课题(GZKP-2022-13)。

摘　　要：类风湿关节炎(RA)是一种对称性小关节累及的自身免疫性疾病,临床上常表现为小关节肿胀、晨僵、进行性疼痛,甚至可见关节畸形、功能缺失。因免疫机制复杂,RA发病机制尚不透彻。但众多研究表明,RA的发病与免疫机制异常、滑膜炎症反应激增、RA纤维样滑膜细胞(RA-FLSs)生物学行为异常、细胞外基质异常降解等方面相关。丝裂原活化蛋白激酶(MAPK)具有调控细胞的生长、增殖、分化和凋亡等多种生物学过程的作用,密切参与RA炎症介质异常释放与活化、RA-FLSs增殖、迁移和侵袭能力异常改变、滑膜血管新生、骨侵蚀和软骨破坏。中医药几千年的实践经验表明,中医药可有效改善RA患者关节肿胀、晨僵、疼痛等临床症状,延缓关节畸形的发生,并具有整体调控、个体化治疗、作用途径、靶点多样、安全性高、不良反应少、质量稳定的特点和优势。同时,现代研究证实中医药可通过干预MAPK信号通路,减少炎症因子、抑制RA-FLSs异常增殖、迁移与侵袭、调控RA-FLSs细胞凋亡、保护细胞外基质等作用,发挥防治RA的作用。该文拟通过综合国内外研究文献,阐述MAPK信号通路在RA发生进展中的关键作用,并总结中药干预MAPK信号通路防治RA的最新研究成果。旨在为开发中药新药及临床应用中药防治RA提供依据。Rheumatoid arthritis(RA)is an autoimmune disease involving symmetrical small joints,with clinical manifestations such as small joint swelling,morning stiffness,progressive pain,and even joint deformity and loss of function.Due to the complex immune mechanism,the pathogenesis of RA remains unclear.However,studies have shown that the pathogenesis of RA is related to abnormal immune mechanism,increased synovial inflammatory response,abnormal biological behavior of RA fibroblast-like synoviocytes(RA-FLSs),and abnormal degradation of extracellular matrix.Mitogen-activated protein kinase(MAPK)plays a key role in the regulation of cell growth,proliferation,differentiation,and apoptosis.It is involved in the abnormal release and activation of inflammatory mediators in RA,the abnormal proliferation,migration,and invasion of RAFLSs,synovial angiogenesis,bone erosion,and cartilage destruction.The thousands of years of practical experience show that Chinese medicine can effectively mitigate the clinical symptoms such as joint swelling,morning stiffness,and pain and delay the occurrence of joint deformity in RA patients.Moreover,the Chinese medicine treatment has the advantages of overall regulation,personalized treatment,multiple pathways and targets,high safety,few adverse reactions,and stable quality.Modern studies have confirmed that Chinese medicine can play a role in the prevention and treatment of RA by interfering in the MAPK signaling pathway,reducing pro-inflammatory cytokines,inhibiting the abnormal proliferation,migration,and invasion of RAFLSs,regulating the apoptosis of RA-FLSs,and protecting extracellular matrix.This article elaborates on the key role of MAPK signaling pathway in the development of RA and reviews the latest research results of Chinese medicine intervention in MAPK signaling pathway for the prevention and treatment RA,aiming to provide a basis for the development of new drugs and the clinical application of Chinese medicine in the prevention and treatment of RA.

关 键 词：丝裂原活化蛋白激酶(MAPK)信号通路 类风湿关节炎 类风湿关节炎纤维样滑膜细胞 中医药 血管生成 炎症反应 细胞凋亡 作用机制 

分 类 号：R2-0[医药卫生—中医学] R22R242R285.5R593.22