基于网络药理学及分子对接技术探讨定喘汤治疗儿童咳嗽变异性哮喘的作用机制

Mechanism of Dingchuan Decoction in the Treatment of Cough Variant Asthma Based on Network Pharmacology and Molecular Docking Technology

目的:通过网络药理学和分子对接技术探讨定喘汤治疗儿童咳嗽变异性哮喘(CVA)的作用机制。方法:基于文献研究和中药系统药理学数据库与分析平台(TCMSP)数据库挖掘定喘汤中各个药物的活性成分,并利用TCMSP数据库预测活性成分作用靶点,借用全球蛋白质资源(Uniprot)数据库校正靶点蛋白对应基因;通过基因卡片(GeneCards)、在线《人类孟德尔遗传》(OMIM)数据库获得CVA的疾病靶点。取药物靶点和疾病靶点的交集靶点并制作韦恩图,运用Cytoscape 3.7.2软件制作"中药-活性成分-靶点"网络并进行网络拓扑分析,利用String数据库构建蛋白互作网络并筛选出核心靶点。基于用于注释、可视化和集成发现的数据库(DAVID)对交集靶点进行基因生物过程分析(GO-BP)和京都基因与基因组百科全书(KEGG)通路富集分析;通过AutoDock Vina和Pymol将得到的核心成分和核心靶点进行分子对接。结果:收集定喘汤复方中活性成分218个,得到相关潜在靶点452个,CVA相关靶点689个,得到交集靶点131个。核心靶点主要为丝氨酸/苏氨酸蛋白激酶1(AKT1)、白细胞介素-6(IL-6)、肿瘤坏死因子(TNF),共有靶点主要富集于PI3K-Akt信号通路、TNF信号通路、Toll样受体信号通路。分子对接结果显示核心成分与靶点具有较好的结合活性。结论:定喘汤治疗CVA具有多成分、多靶点、多通路的特点,为进一步研究定喘汤治疗CVA的作用机制奠定了基础。

Objective:To probe into the mechanism of Dingchuan decoction in the treatment of vough variant asthma(CVA)based on network pharmacology and molecular docking technology.Methods:Literature research and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)were used to obtain the active components of Dingchuan decoction.And the targets of active components were predicted by TCMSP.Uniprot(universal protein resource)database was used to search the corresponding genes of targets.GeneCards and OMIM(online Mendelian inheritance in man)database were used to obtain the disease targets of CVA.Intersection target of drug target and disease target were obtained to make the Venn diagram.Cytoscape 3.7.2 software was used to make the network of“traditional Chinese medicine-active components-targets”and perform the network topology analysis.The protein interaction network was constructed by using String database and the core targets were screened.GO biological process analysis and KEGG pathway enrichment analysis were performed based on DAVID(the database for annotation,visualization and intergrated diacovery).AutoDock Vina and Pymol were used to dock the molecules of the active components with the key targets.Results:A total of 218 active components were found in Dingchuan decoction,and 452 potential targets,689 CVA-related targets and 131 intersection targets were obtained.The main core targets were serine/threonine protein kinase 1(AKT1),interleukin-6(IL-6)and tumor necrosis factor(TNF),and the common targets were mainly enriched in PI3K-Akt signaling pathway,TNF signaling pathway and Toll-like receptor signaling pathway.The results of molecular docking showed that the key components have a good binding activity with the key targets.Conclusion:Dingchuan decoction has the characteristics of multi-components,multi-targets and multi-pathways in the treatment of CVA,which lays a foundation for further study of the mechanism of Dingchuan decoction in the treatment of CVA.