基于LRG1/TGF⁃β信号轴探讨清热活血方调节“炎症-骨破坏”治疗类风湿关节炎的靶向作用机制

Discussion on the Targeting Mechanism of Qingre Huoxue Formula(清热活血方)for Treatment of Rheuma⁃toid Arthritis by Regulating“Inflammation-Bone Destruction”:Based on LRG1/TGF-βSignalling Axis

通过梳理前期相关研究,认为湿热证是类风湿关节炎(RA)的核心证候,清热活血方是治疗RA湿热证的有效方剂。“炎症-骨破坏”是RA的关键病理环节,也是清热活血方疗效的优势环节所在,富含亮氨酸α2糖蛋白1(LRG1)可介导转化生长因子⁃β(TGF⁃β)信号通路参与RA“炎症-骨破坏”病理过程,或可作为清热活血方治疗RA湿热证的疗效靶点蛋白。据此提出科学假说,即清热活血方可能通过靶向调控LRG1所介导的TGF-β信号通路调节“炎症-骨破坏”治疗RA,并设想后续通过临床研究证实清热活血方对LRG1的临床干预效应,通过动物实验明确清热活血方对LRG1/TGF-β信号轴的作用机制以及LRG1/TGF-β信号轴表达与否对清热活血方的疗效影响。

Based on the previous publications,it is believed that damp-heat syndrome is the core syndrome of rheumatoid arthritis(RA),and Qingre Huoxue Formula(清热活血方)is an effective formula for the treatment of damp-heat syndrome of RA.“Inflammation-bone destruction”is a key pathological link of RA,and it is also the advantage of the effectiveness of Qingre Huoxue Formula.Leucine richα-2-glycoprotein 1(LRG1)can mediate the transforming growth factor-β(TGF-β)signalling pathway to participate in the pathogenic process of“inflammationbone destruction”of RA,and it can be used as a target protein in the treatment of damp-heat syndrome of RA by Qingre Huoxue Formula.Accordingly,a scientific hypothesis was proposed that Qingre Huoxue Formula may regulate TGF-βsignalling pathway mediated by LRG1 to improve“inflammation-bone destruction”of RA,and it was envisioned that the clinical effect of Qingre Huoxue Formula on LRG1 could be confirmed through clinical studies,and the mecha⁃nism of action of Qingre Huoxue Formula on the LRG1/TGF-βsignalling axis as well as the influence of the expression or non-expression of the LRG1/TGF-βsignalling axis on the therapeutic effectiveness of Qingre Huoxue Formula could be clarified through animal experiments.