基于信号通路的中药有效成分治疗类风湿关节炎机制研究进展
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摘要
目的:类风湿关节炎是最常见的炎性关节病之一,以滑膜组织增生、关节软骨进行性破坏为主要特征,与功能障碍和寿命缩短显著相关。药物治疗是类风湿关节炎的主要干预手段,但糖皮质激素和免疫抑制剂治疗存在副作用大、起效缓慢和疗效差等缺点,生物制剂治疗又存在价格昂贵的缺点。类风湿关节炎属中医"痹证"范畴,中医中药治疗类风湿关节炎历史悠久,具有疗效好、副作用小等优势,但其机制有待进一步研究。信号通路参与类风湿关节炎的发病和进展,是进行类风湿关节炎的病理机制及治疗药物的相关药理研究的主要靶点之一。近年来,针对中药有效成分对类风湿关节炎信号通路的调控作用开展了大量研究。这些信号通路包括Wnt信号通路,酪氨酸激酶(JAK)信号传导与转录活化因子(STAT)信号通路,丝裂原活化蛋白激酶(MAPK)信号通路,磷脂酰肌醇3激酶(PI3K)/丝氨酸/蛋白激酶B(Akt)信号通路,核转录因子-κB(NF-κB)信号通路,Toll样受体(TLRs)信号通路,细胞NF-κB受体活化因子配体(RANKL)/细胞NF-κB受体活化因子(RANK)/骨保护素(OPG)通路等。通过综述近年研究的成果,以期为类风湿关节炎的基础研究、新药开发及临床治疗提供思路和借鉴。
Objective: Rheumatoid arthritis( RA) is one of the most common inflammatory arthropathy diseases, characterized by synovium hyperplasia and progressive destruction of articular cartilage, which is significantly associated with dysfunction and shortening of life span. Drug therapy is the main intervention for RA,but the glucocorticoid and immunosuppressant have many shortcomings in treatment,such as great side effect,slow onset and poor efficacy,while biological agents are too expensive. RA belongs to the category of " arthralgia syndrome" in traditional Chinese medicine( TCM). TCM treatment for RA has a well-established history and multiple advantages such as good curative effect and less side effects,but its mechanism needs to be further studied. Signaling pathway is involved in the pathogenesis and progression of RA,so it is one of the main targets in research on the pathogenesis of RA and related pharmacological research of therapeutic drugs. In recent years,a large number of studies have been carried out on the regulation effect of active components of TCM on RA signaling pathways. These signaling pathways include Wnt signaling pathway, Janus tyrosine kinase( JAK)-signal transducers and transcription activator( STAT) signaling pathway,mitogen-activated protein kinase( MAPKs)signaling pathway,phosphoinositide-3-kinase( PI3 K)/serine/protein kinase B( Akt) signaling pathway,nuclear factor-kappa B( NF-κB) signaling pathway,Toll like receptor( TLRs) signaling pathway,receptor activator of the nuclear factor kappa B ligand( RANKL)/receptor activator of the nuclear factor kappa B( RANK)/Osteoprotegerin( OPG) signaling pathway and so on. By reviewing the research results in recent years,we hope to provide ideas and reference for the basic research,development of new drugs and clinical treatment of RA.
Objective: Rheumatoid arthritis( RA) is one of the most common inflammatory arthropathy diseases, characterized by synovium hyperplasia and progressive destruction of articular cartilage, which is significantly associated with dysfunction and shortening of life span. Drug therapy is the main intervention for RA,but the glucocorticoid and immunosuppressant have many shortcomings in treatment,such as great side effect,slow onset and poor efficacy,while biological agents are too expensive. RA belongs to the category of " arthralgia syndrome" in traditional Chinese medicine( TCM). TCM treatment for RA has a well-established history and multiple advantages such as good curative effect and less side effects,but its mechanism needs to be further studied. Signaling pathway is involved in the pathogenesis and progression of RA,so it is one of the main targets in research on the pathogenesis of RA and related pharmacological research of therapeutic drugs. In recent years,a large number of studies have been carried out on the regulation effect of active components of TCM on RA signaling pathways. These signaling pathways include Wnt signaling pathway, Janus tyrosine kinase( JAK)-signal transducers and transcription activator( STAT) signaling pathway,mitogen-activated protein kinase( MAPKs)signaling pathway,phosphoinositide-3-kinase( PI3 K)/serine/protein kinase B( Akt) signaling pathway,nuclear factor-kappa B( NF-κB) signaling pathway,Toll like receptor( TLRs) signaling pathway,receptor activator of the nuclear factor kappa B ligand( RANKL)/receptor activator of the nuclear factor kappa B( RANK)/Osteoprotegerin( OPG) signaling pathway and so on. By reviewing the research results in recent years,we hope to provide ideas and reference for the basic research,development of new drugs and clinical treatment of RA.
引文
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[18]Malemud C J.The role of the JAK/STAT signal pathway in rheumatoid arthritis[J].Ther Adv Musculoskelet Dis,2018,10(5/6):117-127.
[19]陈呢喃,张冬青.JAK-STAT信号通路在类风湿关节炎中的研究进展[J].现代免疫学,2013,33(5):425-428.
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[24]YANG Y,DONG Q,LI R.Matrine induces the apoptosis of fibroblast-like synoviocytes derived from rats with collagen-induced arthritis by suppressing the activation of the JAK/STAT signaling pathway[J].Int J Mol Med,2017,39(2):307-316.
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