基于网络药理学分析大黄—枳实药对治疗SAP的作用机制

Study on the Mechanism of Dahuang-Zhishi in Treating Severe Acute Pancreatitis Based on Network Pharmacology

目的:通过运用网络药理学方法探讨大黄-枳实药对治疗重症急性胰腺炎(SAP)多靶点、多通路的作用机制。方法:使用TCMSP数据库对大黄、枳实的活性成分进行筛选,运用PubChem、Swiss Target Prediction数据库进行活性成分的靶点预测,在GeneCards数据库以进行疾病相关靶点检索,通过构建韦恩图得到共同靶点信息,在String平台构建蛋白互作网络(PPI),使用Cytoscape 3.7.2软件分析得到各共同靶点的Degree值、并绘制簇状条形图,再运用Metascape进行GO功能分析和KEGG通路富集分析并可视化处理,最后使用Cytoscape 3.7.2软件构建药物-靶点-通路网络。结果:本研究共筛选到大黄、枳实2味中药29个主要活性成分及335个可能的作用靶点,筛选得到疾病相关靶点604个,经构建韦恩图得到共同靶点86个,对86个关键靶点进行GO功能分析和KEGG通路富集分析,进而构建药物-靶点-通路网络,网络拓扑分析结果显示AKT1、EGFR、MAPK1、PIK3R1等是关键靶点。结论:大黄-枳实药对主要通过AKT1、MAPK1、PIK3R1、EGFR等靶点对SAP发挥治疗效应,可能是通过癌症通路(Pathways in cancer)、PI3K-Akt信号通路(PI3K-Akt signaling pathway)等数条信号通路来调控的。

Objective:To explore the multi-target and multi-path mechanism of Dahuang-Zhishi in the treatment of severe acute pancreatitis by using data mining method of network pharmacology.Methods:Use the TCMSP database to screen the active ingredients in Dahuang-Zhishi,use PubChem and Swiss Target Prediction databases to predict the active ingredients,search for disease-related targets in the GeneCards database,and obtain common results by constructing a Venn diagram.Target information,construct a protein interaction network(PPI)on the String platform,use Cytoscape 3.7.2 software to analyze the Degree value of each common target,draw a clustered bar graph,and then use Metascape to perform GO function analysis and KEGG pathway Enrichment analysis and visual processing,and finally use Cytoscape 3.7.2 software to construct a drug-target-pathway network.Results:In this study,a total of 29 main active ingredients and 335 possible targets of two Chinese medicines including Rhubarb and Citrus aurantium in Dahuang-Zhishi were screened,and 604 disease-related targets were screened.After constructing the Venn diagram,86 common targets were obtained.GO function analysis and KEGG pathway enrichment analysis were performed on 86 key targets,and then the drug-target-pathway network was constructed.The network topology analysis results showed AKT1,EGFR,MAPK1,PIK3 R1 and others are the key targets.Conclusion:Dahuang-Zhishi mainly exerts therapeutic effects on SAP by acting on AKT1,MAPK1,PIK3 R1,EGFR and other targets.These targets may be involved in cancer pathways(Pathways in cancer),PI3 K-Akt signaling pathway(PI3 K-Akt signaling pathway)and other signal pathways.