基于网络药理学探讨黄连温胆汤治疗心律失常的机制

Mechanism of Huanglian Wendan Decoction in treatment of arrhythmia based on network pharmacology

目的通过网络药理学探讨黄连温胆汤治疗心律失常的机制。方法通过TCMSP平台收集黄连温胆汤相关药物的有效成分及作用靶点;经过UniProt获取标准蛋白名并转换靶点基因名;使用DIGSEE、OMIN、Drugbank等数据库收集心律失常疾病基因靶点,合并后去重与复方中药靶点取交集;使用String数据库绘制蛋白相互作用(PPI)网络,使用Cytoscape 3.9.1经过拓扑分析获取核心靶点;使用R语言进行京都基因与基因组百科全书(KEGG)及基因本体(GO)富集分析并对排名靠前的通路进行可视化处理;对KEGG排名靠前的通路使用Cytoscape 3.9.1构建中药成分–靶点–通路图。结果通过拓扑分析得到表皮生长因子受体(EGFR)、丝裂原活化蛋白激酶(MAPK)1、MAPK3、信号转导和转录激活因子3(STAT3)、CAMP反应性元素结合蛋白1(CREB1)、雌激素受体(ESR1)等19个核心靶点;通过KEGG富集分析共得到186条信号通路,黄连温胆汤可能通过晚期搪基化终产物及其受体(AGE-RAGE)、磷脂酰肌醇3-激酶(phosphatidylinositol-3-kinase,PI3K)/蛋白激酶B(protein kinase B,Akt)、MAPK等信号通路对心律失常起治疗作用。结论黄连温胆汤可通过多种目标基因、分子通路治疗心律失常。

Objective To explore the mechanism of Huanglian Wendan Decoction in treatment of arrhythmia based on network pharmacology.Methods The effective components and targets of Huanglian Wendan Decoction were collected by TCMSP platform.The standard protein name was obtained by UniProt and the target gene name was converted.The gene targets of arrhythmia were collected by DIGSEE,OMIN,Drugbank,and other databases.PPI protein interaction network was drawn using String database,and the core target was obtained using Cytoscape 3.9.1 through topological analysis.KEGG and GO enrichment analysis was performed using R language,and the top-ranked pathways were visualized.Cytoscape 3.9.1 was used to construct TCM component-targetpathway map for pathways with high KEGG ranking.Results 19 Core targets including EGFR,MAPK1,MAPK3,STAT3,CREB1,and ESR1 were obtained.A total of 186 signaling pathways were obtained through KEGG enrichment analysis.Huanglian Wendan Decoction may have therapeutic effects on arrhythmia through AGE-RAGE,PI3K-Akt,and MAPK and other signaling pathways.Conclusion Huanglian Wendan Decoction can treat arrhythmia through multiple target gene and molecular pathways.