基于网络药理学研究葶苈大枣泻肺汤治疗心力衰竭的作用机制

Study on Mechanism of Treatment of Heart Failure by Tingli Dazao XiefeiDecoction( 葶苈大枣泻肺汤) Based on Network Pharmacology

目的通过网络药理学方法研究葶苈大枣泻肺汤的活性成分、作用靶点及治疗心力衰竭可能的作用机制。方法采用TCMSP数据库及Swiss Target Prediction数据库获得葶苈大枣泻肺汤的活性成分及作用靶点,通过Uniprot数据库对靶点进行标准化,通过GeneCard、OMIM数据库获得心力衰竭的疾病靶点。将药物的作用靶点与疾病靶点进行交集,获得药物-疾病共同靶点。应用STRING数据库构建蛋白-蛋白相互作用网络图(PPI),并应用R语言对核心靶点进行筛选。采用Cytoscape 3.7.2软件绘制出药物活性成分-心力衰竭靶点网络。最后运用R语言对共同靶点进行基因本体(GO)生物过程分析、京都基因与基因组百科全书(KEGG)通路富集分析。结果本研究共预测到葶苈大枣泻肺汤共39个活性成分,122个与心力衰竭共同的靶点。PPI网络中核心靶点为信号传导及转录激活蛋白-3(STAT3)、蛋白激酶(AKT1)、丝裂原活化蛋白激酶(MAPK)等。GO生物过程结果显示与细胞间信号传导、分子与蛋白结合过程及体内酶活性调节等相关。KEGG通路富集分析结果显示主要涉及AGE-RAGE信号通路(AGE-RAGE signaling pathway in diabetic complications)、流体剪切应力与动脉粥样硬化(Fluid shear stress and atherosclerosis)及MAPK信号通路等方面。结论葶苈大枣泻肺汤治疗心力衰竭具有多成分、多靶点、多通路的特点。该研究为进一步探讨该药治疗心力衰竭的作用机制提供了参考。

Objective To study the active components,target and therapeutic mechanism of Tingli Dazao Xiefei Decoction(葶苈大枣泻肺汤)in the treatment of heart failure by pharmacological method.Method:The active components and targets of Tingli Dazao Xiefei Decoction were obtained by TCMSP database and SwissTargetPrediction database.The target was normalized by Uniprot database,and the target of heart failure was obtained by GeneCard and OMIM database.The target of the drug is intersected with the target of the disease to obtain a common target of the drug-disease.The STRING database was used to construct a protein-protein interaction network map(PPI),and the core target was screened using the R language.The drug active ingredient-heart failure target network was drawn using Cytoscape 3.7.2 software.Finally,using R language to perform gene ontology(GO)biological process analysis on common targets,Kyoto Gene and Genome Encyclopedia.Results A total of 39 active components and 122 common targets for heart failure were predicted in this study.The core targets in the PPI network were signaling and transcriptional activator protein-3(STAT3),protein kinase(AKT1),and mitogen-activated protein kinase(MAPK).The results of GO biological processes were shown to be related to intercellular signaling,molecular-protein binding processes and regulation of enzyme activity in vivo.The results of KEGG pathway enrichment analysis showed that it mainly involved AGE-RAGE signaling pathway in diabetic complications,fluid shear stress and atherosclerosis and MAPK signaling pathway.Conclusion The treatment of heart failure with Tingli Dazao Xiefei Decoction has the characteristics of multi-component,multi-target and multi-channel.This study provides a reference for further exploration of the mechanism of this drug in the treatment of heart failure.