摘要
目的基于“肺虚络瘀”理论及网络药理学与分子对接方法探析中药黄芪-丹参药对配伍治疗肺纤维化的作用机制。方法借助TCMSP,分别以“黄芪”“丹参”为关键词检索药物活性成分及对应靶点,在UniProt蛋白质数据库中将药物成分靶点名称转化为对应基因名;运用OMIM、GeneCards、TTD、DisGeNET等疾病基因数据库,分别检索并筛选肺纤维化疾病的靶点基因。使用venny 2.1在线软件作图工具平台,将药物成分靶点与肺纤维化疾病靶点取交集,获取药物-疾病共同靶点基因,并绘制韦恩图;使用Cytoscape 3.10.0作图软件构建中药-成分-共同靶点-疾病基因网络;再运用String数据库构建其蛋白互作(PPI)网络,同时筛选出核心靶点;运用Metascape数据库对药物-疾病交集靶点进行GO和KEGG富集分析,通过微生信平台对富集结果进行可视化,借助AutoDock 1.5.7软件进行分子对接验证。结果中药黄芪-丹参药对活性成分共85个,核心成分为槲皮素、山柰酚、丹参酮Ⅵ、丹参酮IIA;成分靶点1443个,药物-疾病交集靶点基因共85个,作用于疾病的核心靶点12个;GO富集分析结果分别得到生物过程(BP)1370条,分子功能(MF)91条,细胞组成(CC)60条;KEGG富集分析有169个信号通路;分子对接验证结果显示,小分子配体与蛋白受体之间均有相对稳定的结合力。结论“黄芪-丹参”药对通过槲皮素、山柰酚、丹参酮IIA等多种有效成分,可能通过调控MMP-9、TP-53、TNF、IL-1β、TGF-β1等蛋白表达,从而发挥其抗肺纤维化的作用。
Objective To analyze the mechanism of action of Huangqi(Astragali Radix)-Danshen(Salviae Miltiorrhizae Radix et Rhizoma)in the treatment of pulmonary fibrosis based on the theoretical network pharmacology and molecular docking method of the theory of"lung deficiency and collateral stasis".Methods With the help of Traditional Chinese Medicine Systems Pharma⁃cology Database and Analysis Platform(TCMSP),it searched the active ingredients and the corresponding targets with the key⁃words of"Huangqi(Astragali Radix)"and"Danshen(Salviae Miltiorrhizae Radix et Rhizoma)"respectively,and converted the names of the targets of the drug ingredients into the corresponding gene names in the UniProt Protein Database.OMIM,Gene⁃Cards,TTD,DisGeNET and other disease gene databases were used to search and screen the target genes of pulmonary fibrosis diseases.Venny 2.1 online software was applied for mapping tool platform.The intersection of drug component targets and pul⁃monary fibrosis disease targets were taken to obtain drug-disease common target genes and draw the Wayne diagram.Cytoscape 3.10.0 mapping software was used to construct the traditional Chinese medicine-component-common target-disease gene net⁃work;and String database was used to construct the protein-protein-interaction(PPI)network,and the core targets were screened.At the same time,the core targets were screened out.The Metascape database was used to analyze the GO and KEGG enrichment of drug-disease intersecting targets,and the enrichment results were visualized through the microbiology platform,and molecular docking was verified with the help of AutoDock 1.5.7 software.Results The total number of active ingredients of Huangqi(Astragali Radix)-Danshen(Salviae Miltiorrhizae Radix et Rhizoma)was 85,and the core ingredients were quercetin,kaempferol,tanshinone VI and tanshinone IIA.The number of constituent targets was 1443,and the total number of target genes of drug-disease intersection was 85,and the core targets of disease were 12.The results of GO enri
作者
余琼
于雪峰
YU Qiong;YU Xuefeng(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning,China;The Second Hospital Affiliated to Liaoning University of Traditional Chinese Medicine,Shenyang 110034,Liaoning,China)
出处
《实用中医内科杂志》
2024年第12期75-79,I0026-I0028,共8页
Journal of Practical Traditional Chinese Internal Medicine
基金
国家中医药管理局区域中医诊疗中心项目(20181012)
于雪峰辽宁省名中医传承工作室项目(20220815)。
关键词
黄芪-丹参
“肺虚络瘀”理论
网络药理学
分子对接
肺纤维化
Huangqi(Astragali Radix)-Danshen(Salviae Miltiorrhizae Radix et Rhizoma)
theory of"lung deficiency and collateral stasis"
network pharmacology
molecular docking
pulmonary fibrosis
