基于“肾络癥瘕”理论探讨肾炎防衰液治疗肾间质纤维化的药效物质基础与机制

Study on Material Basis and Mechanism of Shenyan Fangshuai Formula(肾炎防衰液)in the Treatment of Renal Interstitial Fibrosis based on“Sheng Luo Zheng Jia”Theory

目的:运用网络药理学与分子对接探寻肾炎防衰液治疗肾间质纤维化(RIF)的活性成分和作用机制。方法:通过TCMSP平台和BATMAN-TCM数据库筛选肾炎防衰液的活性成分及作用靶点;利用GeneCards数据库、DisGeNET平台获取RIF相关靶点;将两者的共有靶点与其对应的中药成分通过Cytoscape3.7.2软件构建“成分-靶点”网络,利用Centiscape插件筛选出重要的活性成分;通过Clue GO 2.5.4插件对共有靶点进行京都基因与基因组百科全书(KEGG)富集分析,获取肾炎防衰液治疗RIF的潜在作用通路,采用Autodock和PyMol将核心成分和靶点蛋白进行分子对接及可视化处理。结果:肾炎防衰液经筛选后获得200个活性成分,76个参与治疗RIF的潜在靶点,可能通过参与糖尿病并发症的晚期糖基化终末产物(AGE)-晚期糖基化终末产物受体(RAGE)信号通路、流体剪切应力与动脉粥样硬化、肿瘤坏死因子(TNF)信号通路、松弛素信号通路、缺氧诱导因子-1(HIF-1)信号通路、白介素-17(IL-17)信号通路、血管内皮生长因子(VEGF)信号通路、脂肪细胞脂肪分解的调节、磷脂酰肌醇3-激酶(PI3K)-蛋白激酶B(Akt)信号通路、Toll样受体(TLRs)信号通路等途径参与RIF的治疗,分子对接结果提示肾炎防衰液的核心成分与INS、IL-6、ALB、VEGFA、TNF具有较好的亲和力。结论:肾炎防衰液的多种活性成分具改善RIF的作用,该方可能通过抑制炎症反应、调控自噬、调节糖脂代谢等途径延缓RIF的发展。

Objective:To explore the active components and mechanism of Shenyan Fangshuai Formula(肾炎防衰液SYFSF)in the treatment of renal interstitial fibrosis(RIF)by network pharmacology and molecular docking.Methods:TCMSP and BATMAN-TCM were used to screen the active components and targets of SYFSF.Genecards database and DisGeNET platform were used to obtain RIF-related targets.The"component target"network was constructed by Cytoscape 3.7.2,and the important active components were screened by Centiscape.The Kyoto Encyclopedia of genes and genomes(KEGG)enrichment analysis of common targets was carried out by Clue GO 2.5.4 to obtain the potential pathway of nephritis anti-aging liquid in the treatment of RIF.The core components and target proteins were docking and visualized by Autodock and PyMOL.Results:A total of 200 active components and 76 potential targets for RIF treatment were obtained from SYFSF.SYFSF may play a role of the treatment of RIF through AGE-RAGE signaling pathway in diabetic complications,Fluid shear stress and atherosclerosis,TNF signaling pathway,Relaxin signaling pathway,HIF-1 signaling pathway,IL-17 signaling pathway,VEGF signaling pathway,egulation of lipolysis in adipocytes,PI3K-Akt signaling pathway,and Toll-like receptor signaling pathway.The results of molecular docking suggested that the core components of the SYFSF had good affinity with INS,IL6,ALB,VEGFA and TNF.Conclusion:SYFSF had a variety of active components that could inhibit renal interstitial fibrosis.It had therapeutic effect on RIF mainly by inhibiting inflammatory response,regulating autophagy,and regulating glucose and lipid metabolism.