摘要
目的基于网络药理学及分子对接技术探讨当归四逆吴茱萸生姜汤治疗雷诺综合征的作用机制,为临床应用提供理论依据.方法运用TCMSP检索当归四逆吴茱萸生姜汤的活性成分和作用靶点,通过GeneCards、OMIM、PharmGkb、DrugBank数据库收集其靶点.应用Cytoscape 3.6.1软件构建"化合物-靶点"网络,借助STRING平台构建交集靶点的蛋白相互作用(PPI)网络,并使用Cytoscape对网络进行拓扑分析获取核心基因,通过R语言进行基因本体(GO)富集和KEGG通路富集分析,最后将核心基因与当归四逆吴茱萸生姜汤主要成分进行分子对接验证.结果经数据库预测得到当归四逆吴茱萸生姜汤治疗雷诺综合征的有效成分27个,对应靶点86个;拓扑分析得到CXCL8、VEGFA、CASP3、PTGS2等9个核心基因;GO富集分析共涉及到生物过程(BP)1777个,细胞组分(CC)80个,分子功能(MF)128个,KEGG通路富集分析筛选得到136条与雷诺综合征相关通路,从而通过调控炎症、细胞增殖与凋亡等功能发挥重要作用.分子对接结果表明,主要活性化合物能够分别与核心靶点结合,并展现出较好的亲和力.结论本研究对当归四逆吴茱萸生姜汤治疗雷诺综合征的多成分、多靶点、多通路的作用与机制进行初步探讨,以期为后续基础研究提供参考,为临床应用提供理论依据.
Objective To explore the mechanism of Danggui Sini Wuzhuyu Shengjiang decoction in the treatment of Raynaud‘s syndrome based on network pharmacology and molecular docking technology,so as to provide theoretical basis for clinical application.Methods The active components and action targets of Danggui Sini Wuzhuyu Ginger decoction were searched by TCMSP,and the disease targets were collected by GeneCards,OMIM,PharmGkb and DrugBank databases.The“compound-targets”network was constructed by Cytoscape3.6.1 software,and the protein interaction(PPI)network of intersection target was constructed with the help of STRING platform.The core genes were obtained by topological analysis of the network by Cytoscape,and the gene ontology(GO)enrichment and KEGG pathway enrichment were analyzed by R language.Finally,the core genes were docked with the main components of Danggui Sini Wuzhuyu Ginger decoction.Results 27 active components and 86 corresponding targets of Danggui Sini Wuzhuyu Shengjiang decoction in the treatment of Raynaud‘s syndrome were predicted by database,and 9 core genes such as CXCL8,VEGFA,CASP3 and PTGS2 were obtained by topological analysis.GO enrichment analysis involved 1777 biological processes(BP),80 cell components(CC)and 128molecular function(MF).KEGG pathway enrichment analysis identified 136 pathways related to Raynaud‘s syndrome,including AGEs-RAGE signal pathway,tumor necrosis factor signal pathway,relaxin signal pathway,hypoxia inducible factor signal pathway,NF-κB signal pathway and so on.Centralized regulation of inflammation,pannus formation,cell proliferation and apoptosis plays an important role.The results of molecular docking showed that the main active compounds could bind to the core targets and showed good affinity.Conclusion This study preliminarily discusses the effect and mechanism of multi-component,multi-target and multi-pathway of Danggui Sini Wuyu Shengjiang decoction in the treatment of Raynaud‘s syndrome,in order to provide reference for follow-up basic research and provide theoretical basis for clinical application.
作者
周志锋
郭会卿
曹玉举
赵晶晶
袁都户
ZHOU Zhi-feng;GUO Hui-qing;CAO Yu-ju;ZHAO Jing-jing;YUAN Du-hu(Henan University of Traditional Chinese Medicine,Zhengzhou,Henan 450000;Henan Hospital of Traditional Chinese Medicine,Zhengzhou,Henan 450000;Zhengzhou Traditional Chinese Medicine Orthopaedic Hospital,Zhengzhou,Henan 450000)
出处
《智慧健康》
2021年第22期164-169,共6页
Smart Healthcare
基金
河南省中医药重点实验室建设项目(豫卫中医函[2021]30号)。
关键词
雷诺综合征
当归四逆吴茱萸生姜汤
网络药理学
分子对接
Raynaud’s syndrome
Danggui Sini Wuzhuyu Ginger decoction
Network pharmacology
Molecular docking
