海南医科大学学报

目的:基于网络药理学方法探析经典药对"陈皮-半夏"治疗冠脉微循环障碍(coronary microvascular dysfunction,CMD)的主要活性成分、主要靶点基因、关键通路及其作用机制。方法:本研究通过TCMSP数据库获取"陈皮-半夏"药对的主要活性成分及其靶点,筛选其活性成分及潜在靶点。通过Gencards和OMIM数据库获取CMD的主要靶点。运用uniprot数据库查询相对应的基因名称。利用韦恩图取交集可获得"陈皮-半夏"药对治疗冠脉微循环障碍的关键交集靶点。利用String平台进行蛋白质相互作用分析,构建PPI网络并通过Cytoscape3.7.1软件进一步挖掘网络中潜在的蛋白质功能模块。在DAVID数据库进行靶点基因(GO)功能富集分析和(KEGG)通路富集分析,使用在线绘图工具Bioinformatics网站分别绘制高级气泡图。最后采用Cytoscape3.7.1软件构建"陈皮、半夏成分-冠脉微循环障碍靶点-通路"网络。结果:构建的"陈皮、半夏成分-冠脉微循环障碍靶点-通路"网络中包括柚皮素、诺比林、黄芩素、β谷甾醇等16个药对活性成分,AKT1、VEGFA、BCL2、BAX、JUN等56个预测靶点基因,心血管系统相关通路(PI3K-AKT signaling pathway)、炎症相关通路(TNF signaling pathway)、血管内皮生长因子信号相关通路(VEGF signaling pathway)、细胞凋亡相关通路(Apoptosis)和低氧细胞应激信号通路(HIF-1 signaling pathway)等20条关键通路。结论:应用网络药理学验证了"陈皮-半夏"药对多成分、多靶点、整体调节的作用特点,推测其主要通过保护冠脉微循环内皮细胞功能、抑制细胞凋亡、影响炎性反应等途径发挥治疗冠脉微循环障碍的作用。

Objective:To study the main active compounds,main target genes,critical path and mechanism of the two classical Chinese herbs Chenpi-Banxia in the treatment of coronary microvascular dysfunction(CMD)on the basis of network pharmacology. Methods:Potential active compounds of Chenpi-Banxia from TCMSP were obtained,while the targets for CMD were obtained from DrugBank and OMIM databases.The corresponding gene name was searched using Uniprot database.The key target of Chenpi-Banxia in the treatment of CMD could be obtained by using the intersection of VENNY.The PPI network was screened for the major targets by String and Cytoscape3.7.1.The GO enrichment analysis and KEGG pathway of major targets were performed by using the DAVID database and Binformatics to draw bubble map. Finally,the ingredient-major target-key pathway network was constructed by Cytoscape3.7.1. Results:There were 16 compounds such as naringenin,nobiletin,baicalein.beta-sitosterol etc,and56 predictive target genes such as AKT1、VEGFA、BCL2、BAX、JUN etc,as well as 20 key pathways including inflammation-related pathway(TNF signaling pathway),pathways related to cardiovascular system(PI3 K-Akt signaling pathway),vascular endothelial growth factor signaling pathway(VEGF signaling pathway),apoptosis related pathways(Apoptosis)and hypoxia cell stress signaling pathway(HIF-1 signaling pathway)in the compounds-target-pathway network.Conclusion:The study verifies the characteristics of multi-components,multi-targets and integral regulation for Chenpi-Banxia with the application of network pharmacology. It is predicted that Chenpi-Banxia could treat CMD mainly by protecting endothelial cell function of coronary microcirculation,inhibiting cell apoptosis and affecting inflammatory reaction.