基于网络药理学和分子对接技术探讨芪术肺纤汤治疗特发性肺间质纤维化的作用机制  

Mechanism of Qizhufeixian Decoction in the Treatment of Idiopathic Pulmonary Fibrosis Based on Network Pharmacology and Molecular Docking

作　　者：张雯静 王秋铭 李萌[1] 刘世刚[1] 高扬[1] 李辉[1] 李国勤[1] ZHANG Wenjing;WANG Qiuming;LI Meng;LIU Shigang;GAO Yang;LI Hui;LI Guoqin(Dept.of Respiratory,Guang’anmen Hospital of China Academy of Chinese Medical Sciences,Beijing 100053,China)

机构地区：[1]中国中医科学院广安门医院呼吸科,北京100053

出　　处：《中国医院用药评价与分析》2024年第2期140-146,共7页Evaluation and Analysis of Drug-use in Hospitals of China

基　　金：国家自然科学基金青年科学基金项目(No.82004347);中央本级重大增减支项目:名贵中药资源可持续利用能力建设项目(No.2060302);中央高水平中医医院临床研究和成果转化能力提升项目(No.HLCMHPP2023023)。

摘　　要：目的:采用网络药理学方法和分子对接技术,探讨芪术肺纤汤治疗特发性肺间质纤维化(IPF)的作用机理。方法:利用中药系统药理学数据库与分析平台、中医药百科全书数据库和本草组鉴数据库等检索芪术肺纤汤各个药物的活性成分及靶点;在GeneCards、Drugbank、人类孟德尔遗传综合数据库和DisGeNET数据库中检索IPF的疾病靶点;利用Venny 2.1.0在线软件获取交集靶点,使用STRING数据库和Cytoscape软件绘制芪术肺纤汤治疗IPF的核心靶点蛋白质-蛋白质相互作用(PPI)图;运用DAVID数据库和Metascape数据库对交集靶点进行基因本体(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析;通过Cytoscape软件构建中药-成分-靶点-疾病图和中药-成分-靶点-疾病-通路图;最后将活性成分及核心靶点进行分子对接。结果:共获取芪术肺纤汤活性成分445个,靶点4 705个,IPF疾病靶点4 509个,两者交集靶点456个。利用PPI网络筛选到101个核心靶点;GO、KEGG富集分析分别得到1 148、196个富集结果;熊果酸、芹菜素、木犀草素和槲皮素等成分与核心靶点肿瘤蛋白p53(TP53)、肿瘤坏死因子(TNF)、蛋白激酶B(Akt)1、白细胞介素(1L)1β、IL-6和血管内皮生长因子A(VEGFA)等结合能力较强。结论:芪术肺纤汤可能通过熊果酸、芹菜素、木犀草素和槲皮素等成分与TP53、TNF、Akt1、1L-1β、IL-6和VEGFA等靶点结合,调控磷脂酰肌醇3激酶-Akt等信号通路,发挥治疗IPF的作用,为中医药治疗IPF提供了支持和参考。OBJECTIVE:To probe into the mechanism of Qizhufeixian decoction in the treatment of idiopathic pulmonary fibrosis(IPF)by adopting network pharmacy and molecular docking technology.METHODS:TCMSP,OBJECTIVE:To probe into the mechanism of Qizhufeixian decoction’s treatment for idiopathic pulmonary fibrosis(IPF)utilizing network pharmacology and molecular docking approaches.METHODS:TCMSP,ETCM and HERB databases were retrieved for the active components and targets of various drugs in Qizhufeixian decoction.GeneCards,Drugbank,OMIM and DisGeNET databases were retrieved for the disease targets of IPF.Venny 2.1.0 online software was used to acquire the intersection targets,STRING database and Cytoscape software were used to draw the protein-protein interaction(PPT)map of the core targets of Qizhufeixian decoction in the treatment of IPF.Venny 2.1.0 online software was used to acquire the intersection targets,by using STRING database and Cytoscape software,the protein-protein interaction(PPI)diagram of the core targets of Qizhufeixian decoction in treating IPF was drawn.DAVID database and Metascape database were used to perform gene ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis on the intersection targets.Cytoscape software was used to construct drug-ingredient-targets-disease diagram and drug-ingredient-target-disease-pathway diagram;the molecular docking was finally performed on active components and core targets.RESULTS:A total of 445 active components,4705 targets,4509 IPF disease targets and 456 intersection targets of Qizhufeixian decoction were obtained.A total of 101 core targets were screened by PPI network;1148 and 196 enrichment results were obtained from GO and KEGG enrichment analysis,respectively;the components of ursolic acid,apigenin,luteolin and quercetin had strong binding ability to the core targets of tumor protein p53(TP53),tumor necrosis factor(TNF),protein kinase B(Akt)1,interleukin(IL)1β,IL-6 and vascular endothelial growth

关 键 词：李国勤 芪术肺纤汤 特发性肺间质纤维化 网络药理学 分子对接 

分 类 号：R932[医药卫生—生药学] R96[医药卫生—药学]