基于网络药理学及分子对接技术探讨运脾泻肺化痰汤治疗支气管哮喘的作用机制  

Effects of Spleen-invigorating Lung-purging Phlegm-resolving Decoction on Bronchial Asthma Based on Network Pharmacology and Molecular Docking

作　　者：许欢 陈竹 陈华 陈娜 张芷瑞 XU Huan;CHEN Zhu;CHEN Hua;CHEN Na;ZHANG Zhirui(Fuzhou Hospital of Traditional Chinese Medicine,Fuzhou 344001,China;Guizhou University of Traditional Chinese Medicine,Guiyang 550001,China)

机构地区：[1]抚州市中医医院,江西抚州344001 [2]贵州中医药大学,贵州贵阳550001

出　　处：《西部中医药》2025年第1期80-87,共8页Western Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金(81860868);贵州省中医儿科诊疗中心建设项目(黔中医药函[2021]58号)。

摘　　要：目的:运用网络药理学和分子对接技术分析运脾泻肺化痰汤治疗支气管哮喘(简称哮喘)的作用机制。方法:通过中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)、Swiss Target Prediction数据库,检索运脾泻肺化痰汤各中药的有效活性成分及潜在靶点。通过人类基因数据库(the human gene database,GeneCards)、在线人类孟德尔遗传数据库(online mendelian inheritance in man,OMIM)、Drugbank、药物靶标数据库(therapeutic targetdatabase,TTD)、PharmGKB数据库检索“Bronchial asthma”和“Bronchial asthma in children”关键词,获得哮喘的相关靶基因,并与药物有效成分的靶点相映射得到共同靶点。利用Cytoscape 3.8.2构建运脾泻肺化痰汤-活性有效成分-作用靶点-生物学功能网络图,借助STRING数据库构建蛋白互作网络(protein-protein interactions,PPI)。通过Metascape数据库对靶点进行京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)通路富集分析。结果:运脾泻肺化痰汤与哮喘相关基因取交集后得到288个共同靶点。通过STRING数据库分析得出288个靶点可以发生相互作用,产生了1803条代表蛋白之间相互作用的边,平均自由度为12.5,平均介数为<1.0e-16。推测出运脾泻肺化痰汤治疗哮喘的核心靶点是STAT3、MAPK1、MAPK3、SRC。KEGG通路富集分析结果表明显著富集的通路有176条,其中PI3K/Akt、MAPK、Th17/IL17、TNF、JAK/STAT信号通路等11条可能是运脾泻肺化痰汤治疗哮喘的核心信号通路。分子对接结果表明,运脾泻肺化痰汤中的活性成分与关键靶点具有较高的结合能力。结论:运脾泻肺化痰汤最有可能通过调控PI3K/Akt信号通路治疗哮喘。Objective:To analyze the mechanism of spleen-invigorating lung-purging phlegm-resolving decoction(Yunpi Xiefei Huatan Tang)in the treatment of bronchial asthma based on network pharmacology and molecular docking technology.Methods:The active ingredients of different herbs in the decoction and the potential targets were searched from TCMSP and Swiss Target Prediction database."Bronchial asthma"and"bronchial asthma in children"as the keywords were retrieved from GeneCards,OMIM,TTD and PharmGKB database to obtain the related target genes for asthma,and map them to the targets of the active ingredients of the drug to obtain the common targets.Cytoscape 3.8.2 was applied to construct the network of spleen-invigorating lung-purging phlegm-resolving decoction-active ingredients-the targets of action-biological function,and to build PPI via String database.KEGG pathway enrichment analysis of the targets was performed via Metascape database.Results:All 288 common targets were obtained from the intersection of the decoction with asthma-related genes by analysis.The analysis of the STRING database yielded 288 targets that could interact,generating 1,803 edges representing interactions between proteins with an average degree of freedom of 12.5 and an average median of<1.0e-16.It was concluded that the core targets for the treatment of asthma with the decoction contained STAT3,MAPK1,MAPK3 and SRC.The results of KEGG pathway enrichment analysis demonstrated that 176 pathways were significantly enriched,among them,11 pathways including PI3K/Akt signaling pathway,MAPK signaling pathway Th17/IL17,TNF signaling pathway,JAK/STAT signaling pathway and others might be the core pathways for the treatment of asthma with the decoction.The results of molecular docking showed that the active ingredients of the decoction presented higher binding ability with the key targets.Conclusion:The decoction could treat asthma possibly through regulating PI3K/Akt signaling pathway.

关 键 词：支气管哮喘 运脾泻肺化痰汤 网络药理学 分子对接 信号通路 

分 类 号：R256.1[医药卫生—中医内科学]