类风湿关节炎中医古籍研究及网络药理分析

Research of the medication rule for rheumatoid arthritis based on Traditional Chinese Medicine Ancient Books and Network Pharmacological Analysis

目的探讨传统中医药治疗类风湿关节炎(RA)的用药规律,并用复杂网络药理学的方法阐释其治疗机制。方法检索《中华医典》获取治疗RA中药数据库,对纳入的高频药物使用SPSS Modeler 18.0、SPSS Statistics 26软件进行关联和聚类分析,运用中药系统药理学数据库与分析平台(TCMSP)筛选出高频药物的活性成分,整理TCMSP、瑞士靶点预测数据库(Swiss Target Prediction)、人类基因和网络功能分析数据库(GenCLiP 3.0)中RA的潜在治疗靶点,将药物和疾病靶点进行一一映射,了解作用靶点,通过注释、可视化和集成发现数据库(DAVID)对其进行京都基因与基因组百科全书(KEGG)通路富集分析,并借助功能蛋白协作网络(STRING)数据库和Cytoscape软件构建“药物-成分-靶点-通路-疾病”模型和蛋白互作模型。结果共纳入585首方剂,主要药物分类为解表药、活血化瘀药,通过关联和聚类分析方法发现常用药对为当归-川芎,筛选出其9个活性成分,9个作用靶点,主要通过调控9条主要信号通路发挥其治疗RA的作用。结论RA治疗多以活血化瘀药为主,临床可配伍加减解表药和补虚药。其中,常见药对当归-川芎治疗RA的作用机制主要可能与调控肿瘤坏死因子(TNF)信号通路、Janus激酶/信号转导和转录激活因子(JAK-STAT)信号通路、血管内皮生长因子(VEGF)信号通路、B细胞受体信号通路等信号通路有关。

Objective To explore the medication rule of traditional Chinese medicine(TCM)for rheumatoid arthritis(RA)and explain its therapeutic mechanism with the method of complex network pharmacology.Methods The database of Chinese Medical Classics was searched,and the association and cluster analysis of the included high-frequency drugs about RA were carried out by using SPSS Modeler 18.0 and SPSS Statistics 26 software.The active components of high-frequency drugs were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the potential targets about RA in TCMSP,Swiss Target Prediction and GenCLiP 3.0 databases were sorted out.The drug and disease target were performed in one-to-one mapping,the Kyoto Encyclopedia of Genes and Genomes(KEGG)metabolic pathway was analyzed by Database for Annotation,Visualization and Integrated Discovery(DAVID),and the drug-component-target-pathway model and protein interaction model were constructed with the help of STRING data base and Cytoscape software.Results A total of 585 prescriptions were included,and the main drugs were classified as table-relieving drugs,activating blood circulation and removing blood stasis drugs.It was found that the commonly used drug pair was Angelica sinensis-Ligusticum chuanxiong by correlation and cluster analysis.9 active components and 9 targets were screened,which played a role in the treatment of RA by regulating 9 main signal pathways.Conclusion RA is mainly treated with drugs of promoting blood circulation and removing blood stasis(Angelica sinensis-Ligusticum chuanxiong),which can be combined with relieving surface drugsand tonifying deficiency drugs.Of which,the mechanism of action of Angelica sinensis-Ligusticum chuanxiong for RA may be related to the regulation of Tumor Necrosis Factor(TNF)pathway,Janus kinase/signal transduction and activator of transcription(JAK-STAT)signaling pathway,vascular endothelial growth factor(VEGF)signaling pathway,B cell receptor(BCR)signaling pathway and other signal pathways.