基于“关键成分-效应靶点-核心通路”关联网络分析的三妙丸治疗类风湿性关节炎分子机制研究

Molecular Mechanism of Sanmiao Pill in Treatment of Rheumatoid Arthritis Based on Correlation Network Analysis of"Key Component-effect Target-core Pathway"

目的:采用“关键成分-效应靶点-核心通路”关联网络分析方法探索三妙丸治疗类风湿性关节炎(RA)的潜在作用机制。方法:基于中药数据库分析方法,以口服生物利用度(OB)≥30%、类药性(DL)≥0.18作为筛选条件,寻找三妙丸主要活性成分和相关作用靶点。用CTD网络分析平台及人类基因和基因表型综合数据库获得RA作用靶点,利用Cytoscape 3.7.1软件中的Merge功能筛选交集共有靶点。将共有靶点输入STRING系统构建靶点蛋白相互作用(PPI)网络,通过聚类分析筛选效应靶点,采用WebGestalt富集分析靶点功能及信号通路,并构建“关键成分-效应靶点-核心通路”关联网络。结果:筛选得到三妙丸中60个化学成分,作用于RA的59个靶点,其中效应关键靶点共15个,包括前列腺素G/H合成酶2(PTGS2)、髓过氧化物酶(MPO)、肿瘤坏死因子(TNF)等,与炎症反应、防御反应及细胞因子调节等生物过程紧密相关,可通过调节细胞因子与受体的相互作用、白细胞介素-17(IL-17)信号通路、T细胞受体信号等通路发挥其治疗RA的作用。结论:三妙丸能通过多成分、多靶点、多通路起到治疗RA的作用,为三妙丸的有效性评价、效应机制研究提供参考。

Objective:To explore the mechanism of Sanmiao Pill in the treatment of rheumatoid arthritis(RA)by using the"key component-core target-important pathway"association network model.Methods:Based on the analysis method of traditional Chinese medicine database,the oral-bioavailability(OB)≥30% and drug-likeness(DL)≥0.18 were used as screening conditions to find the main active components and related targets of Sanmiao Pill.The CTD network analysis platform and the human gene and gene phenotype comprehensive database were used to obtain RA targets,and the Merge function in Cytoscape 3.7.1 software was used to screen the intersection common targets.The common target was input into the STRING system to construct the target PPI network,the core target was screened by cluster analysis,the target function and signal pathway were analyzed by WebGestalt enrichment,and the"key component-effect target-core pathway"association network was constructed.Results:60 medicinal components of Sanmiao Pill were screened and applied to 59 targets of RA,including 15 key target of effect,including prostaglandin G/H synthetase 2(PTGS2),pith peroxidase(MPO)and tumor necrosis factor(TNF)are closely related to biological processes such as inflammatory response,defense response and cytokine regulation,and can regulate the interaction between cytokines and receptors,IL-17 signaling pathway.The T cell receptor signal and other pathways play a role in the treatment of RA.Conclusion:Sanmiao Pill can treat RA through multi-component,multi-target and multi-channel.This study provides a scientific basis for the evaluation of the effectiveness and mechanism of Sanmiao Pill.