“新塔花-丹参-降香”配伍治疗心肌缺血损伤分子机制的网络药理学和分子对接研究

A Network Pharmacology and Molecular Docking Study on the Mechanism of“Xintahua-Danshen-Jiangxiang"”in Improving Myocardial Ischemia Injury

目的 通过网络药理学和分子对接技术探讨“新塔花-丹参-降香”改善心肌缺血损伤的药效物质基础和分子作用机制。方法 借助TCMSP、UniProt和PubChem数据库及文献补充获得“新塔花-丹参-降香”的主要活性成分,并将与活性成分相联系的靶基因借助UniProt数据库翻译成相应基因。利用GeneCards、OMIM和TTD数据库得到疾病相关靶点,对主要活性成分与疾病靶点取交集后采用DAVID数据库进行基因本体(GO)功能以及京都基因与基因组百科全书(KEGG)富集分析。最后通过AutoDock Vina软件对关键靶点和主要活性成分进行分子对接验证。结果 筛选“新塔花-丹参-降香”针对心肌缺血损伤的101个活性成分和338个潜在作用靶点。蛋白质-蛋白质相互作用(PPI)网络拓扑分析筛选得到关键靶点白细胞介素-17(IL-17)、HIF-1、核转录因子-κB(NF-κB)、TNF等。GO功能分析发现“新塔花-丹参-降香”生物过程集中在RNA聚合酶Ⅱ启动子的转录正调控、基因表达的正向调控、凋亡过程的负调控、对外源刺激的反应等多个方面。KEGG信号富集分析显示涉及血脂与动脉粥样硬化、糖尿病并发症中的AGE-RAGE信号通路、TNF信号通路、细胞凋亡、IL-17信号通路、前列腺癌、HIF-1信号通路、cAMP信号通路、NF-κB信号通路、mTOR信号通路等。分子对接显示活性物质与靶点蛋白之间存在较强的结合力,其中槲皮素与TNF的结合力最强。结论“新塔花-丹参-降香”配伍治疗心肌缺血损伤具有多成分、多靶点、多通路相互协同的特点,可为防治心肌缺血损伤的研究提供参考。

Objective:To explore the pharmacological substance basis and molecular mechanism of“Xintahua-Danshen-Jiangxiang”in improving myocardial ischemic injury through network pharmacology and molecular docking technology.Methods:Using TCMSP,UniProt,and PubChem databases and literature supplementation,the main active ingredients of“Xintahua-Danshen-Jiangxiang”were obtained,and the target genes associated with the active ingredients were translated into corresponding genes using the UniProt database.Disease-related targets were obtained using GeneCards,OMIM and TTD databases.The main active ingredients were intersected with disease targets,and the DAVID database was used for gene ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.Finally,molecular docking validation was performed on key targets and major active ingredients using AutoDock Vina software.Results:A total of 101 active ingredients and 338 potential targets of“Xintahua-Danshen-Jiangxiang”were screened for myocardial ischemic injury.Protein protein interaction(PPI)network topology analysis screened key targets such as IL-17,HIF-1,NF-kB,TNF,etc.GO functional analysis found that the biological process of“Xintahua-Danshen-Jiangxiang”was concentrated in muliple aspects,including the transcriptional positive regulation of RNA polymerase II promoter,positive regulation of gene expression,negative regulation of apoptosis process,and response to external stimuli.KEGG signal enrichment analysis showed that AGE-RAGE signaling pathway,TNF signaling pathway,apoptosis,IL-17 signaling pathway,prostate cancer,HIF-1 signaling pathway,cAMP signaling pathway,NF-kB signaling pathway,mTOR signaling pathway and other signaling pathways involved in blood lipids and atherosclerosis,diabetes complications.Molecular docking showed a strong binding affinity between the active substance and the target protein,with quercetin having the strongest binding afinity with TNF.Conclusion:The combination of“Xintahua-Danshen-Jiangxiang”in the treatment of myocardial ischemic injury has the characteristics of multi-component,multi-target,and multi pathway synergy,providing reference for research on the prevention and treatment of myocardial ischemic injury.