基于数据挖掘、网络药理学和分子对接探究中医药治疗房颤的核心中药及机制

The Core Traditional Chinese Medicines and Mechanism of Traditional Chinese Medicine Treatment of Atrial Fibrillation Based on Data Mining,Network Pharmacology and Molecular Docking

本研究主要挖掘数据,分析中药治疗房颤的用药规律,并通过网络药理学、分子对接及分子动力学方法探究其核心药对机制。检索知网、维普等数据库的中医药治疗房颤的临床资料,运用SPSS Modeler 18.0进行关联规则分析房颤用药规律;通过TCMSP数据库、OMIM和DrugBank等数据库分析核心药对的活性成分及潜在靶点,构建房颤靶点-活性成分-药物网络;通过String数据库得到房颤核心靶点PPI网络,以及使用Metascape进行GO生物功能分析和KEGG通路分析;对关键成分与关键靶点进行分子对接验证,最后进行分子动力学模拟。结果显示:治疗房颤用药频率前五分别是丹参、炙甘草、麦冬、桂枝和当归,高频药对有“丹参-苦参”、“麦冬-五味子”等。对“丹参-苦参”核心药分析发现其通过槲皮素、木犀草素和丹参酮ⅡA等关键成分作用于房颤AKT1、TNF、IL-6、VEGFA、IL-1β和CASP3核心靶点,参与NF-κB信号通路、cGMP-PKG信号通路和AMPK等通路。分子对接显示,槲皮素、木犀草素、丹参酮ⅡA与AKT1、CASP3、IL-1β等靶点紧密结合,AKT1-丹参酮ⅡA为结合亲和力最高的复合物,分子动力学模拟发现,蛋白-配体构象在40 ns形成稳定构象,并在活性位点形成了氢键。治疗房颤中药主要有丹参、麦冬和桂枝等,关键成分丹参酮ⅡA可能通过调控AKT1等关键靶点治疗房颤,参与NF-κB信号通路、cGMP-PKG信号通路和AMPK等通路,并在调控离子通道和影响炎症因子释放等方面发挥治疗房颤的作用。

Data mining was used to explore the medication rule of traditional Chinese medicine(TCM)in the treatment of atrial fibrillation(AF).The mechanism of its core drug pairs was explored by network pharmacology,molecular docking,and molecular dynamics simulation methods.Effective clinical research data on TCM treatment of atrial fibrillation were collected from CNKI,VIP database and so on.Besides,SPSS Modeler 18.0 was used to analyze the association rules of TCM prescription drugs and medication rules of TCM in the treatment of atrial fibrillation.The active components and potential targets of the core drug pairs were obtained by using TCMSP database,OMIN,and DrugBank database and so on.The network of"atrial fibrillation target-active component-drug was constructed.The core targets of AF were obtained by using the String database.Then,the intersection targets were imported into Metascape databases for GO function analysis and KEGG pathway analysis.Molecular docking technology and molecular dynamics simulation were used to validate the interaction between the core targets and core components.Results showed:the top five frequency of medication in the treatment of AF is Salvia Miltiorrhiza Bunge,Glycyrrhizae,Ophiopogon Japonicus,Cinnamomum Cassia Presl,and Angelicae Sinensis Radix.The core drug pairs with the higher confidence were"Salvia Miltiorrhiza Bunge-Radix Sophorae Flavescentis",“Ophiopogon Japonicus-Schisandra Chinensis”and so on.The network pharmacology analysis of the core drug pair of"Ophiopogon Japonicus-Schisandra Chinensis"showed that it acted on core targets such as AKT1,TNF,IL-6、VEGFA,IL-1β,and CASP3 through key components such as quercetin,luteolin,tanshinone IIA,and participated in biological processes such as NF-κB signaling pathway,cGMP-PKG signaling pathway,AMPK signaling pathway.Molecular docking showed that quercetin,luteolin and tanshinone IIA have good binding activity with AKT1,CASP3,IL-1β and so on.The compound of AKT1 and tanshinone IIA has the best binding activity.Molecular dynamics simulation showed that the compound had a stable conformation in 40 ns and hydrogen bonds in the active site.Traditional Chinese medicine in the treatment of atrial fibrillation mainly includes Salvia Miltior-rhiza Bunge,Ophiopogon Japonicus,etc.The key components of tanshinoneⅡA may regulate the treatment of atrial fibrillation through the regulation of AKT1 and other key targets,participate in the NF-κB signaling pathway,cGMP-PKG signaling pathway,AMPK and other pathways to regulate ion channels and affect the release of inflammatory factors,playing a role in the treatment of atrial fibrillation.