中药干预类风湿关节炎相关信号通路研究进展

Traditional Chinese Medicine Intervention in Rheumatoid Arthritis-related Signaling Pathways:A Review

类风湿关节炎(RA)作为一种自身免疫性疾病,主要以持续性滑膜炎症为其主要特征,常对称性的累及多个关节,严重时可导致关节畸形、关节功能丧失甚至残疾。RA发病机制复杂,防治复杂,彻底治愈困难。既往研究证实,控制炎症过程的核转录因子-κB(NF-κB)信号通路、调节氧化应激、抑制炎症、维护细胞稳态的核因子E_(2)相关因2(Nrf2)/血红素氧合酶-1(HO-1)信号通路、在细胞生长、分化、凋亡及炎症反应中发挥关键作用的Wnt/β-连环蛋白(β-catenin)信号通路、抗炎、抗氧化、调控滑膜细胞的沉默信息调节因子1(SIRT1)信号通路、抗炎、调控能量代谢的腺苷酸活化蛋白激酶(AMPK)信号通路、与RA中的血管生成相关的缺氧诱导因子-1α(HIF-1α)/血管内皮生长因子(VEGF)信号通路均是防治RA的重要靶点与机制。同时,众多研究证实,中医药通过调控上述信号通路,发挥上述信号通路的相关作用来防治RA,并展现了中医药调控途径多、长效、不良反应少等优势。兹该文通过查阅众多研究报道,阐述了上述信号通路在RA中的作用,并详细总结了以近年来中药干预上述信号通路防治RA的最新研究成果,旨在推动对RA发病机制和中药治疗的深入研究,为中药的合理应用提供科学依据,更是为未来治疗RA的新药物研发和临床实践提供有益的启示。

Rheumatoid arthritis(RA),as an autoimmune disease,is mainly characterized by persistent synovitis.It often involves multiple joints symmetrically and can lead to joint deformity,joint function loss,and even disability in severe cases.The pathogenesis of RA is complex,and the prevention and treatment are complicated.Therefore,it is difficult to cure the disease completely.Previous studies have validated important targets and mechanisms for the prevention and treatment of RA,including the nuclear factor-κB(NF-κB)signaling pathway that controls the inflammatory process,nuclear factor E_(2)-related factor 2(Nrf2)/heme oxygenase-1(HO-1)signaling pathway that regulates oxidative stress,inhibits inflammation,and maintains cell homeostasis,Wnt/β-catenin signaling pathway that plays a key role in cell growth,differentiation,apoptosis,and inflammatory response,anti-inflammatory,anti-oxidation,and silent information regulator 1(SIRT1)signaling pathway that regulates synovial cells,anti-inflammatory adenylate-activated protein kinase(AMPK)signaling pathway that regulates energy metabolism,and hypoxia-inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)signaling pathway related to angiogenesis in RA.At the same time,many studies have confirmed that traditional Chinese medicine prevents and treats RA by regulating the above signaling pathways and exerting their related effects,indicating the advantages of traditional Chinese medicine such as multiple regulatory pathways,long-term effects,and less adverse reactions.In this paper,by consulting many research reports,the role of the above-mentioned signaling pathways in RA was clarified,and the latest research results of traditional Chinese medicine intervention in the above-mentioned signaling pathways in the prevention and treatment of RA in recent years were summarized in detail.This paper aims to promote the in-depth study of the pathogenesis of RA and its treatment with traditional Chinese medicine,provide a scientific basis for the rational application of traditional Chinese medicine,and offer useful enlightenment for the development of new drugs and clinical practice for the treatment of RA in the future.