基于网络药理学与分子对接探究附子-丹参治疗病态窦房结综合征的药理机制

To Explore the Mechanism of Monkshood-Salvia Miltiorrhiza in the Treatment of Sick Sinus Syndrome Based on Network Pharmacology and Molecular Docking

目的利用网络药理和分子对接技术,探究附子-丹参药对治疗病态窦房结综合征(sick sinus syndrome,SSS)的作用机制。方法通过TCMSP数据库检索并筛选附子、丹参的有效成分及其对应靶点;利用DisGeNET、GeneCards、OMIM数据库预测SSS治疗靶点;借助韦恩图取交集,然后利用String数据库及Cytoscape 3.7.2进行PPI网络分析,通过拓扑分析得到关键靶点,利用Metascape数据库对靶点进行GO功能及KEGG富集分析,使用AutoDock软件对疾病核心靶基因与潜在活性成分进行分子对接,对接结果通过Pymol软件可视化。结果共挖掘出64种活性成分,77个靶点与改善SSS相关。治疗SSS的重要靶点涉及AKT1、TP53、IL-6、TNF、VEGFA等,主要作用于脂质和动脉粥样硬化通路、松弛素信号通路、钙信号通路、cAMP信号通路、NF-κB信号通路、细胞凋亡、脂肪细胞脂肪分解等信号通路。分子对接结果显示核心成分和核心靶点之间可稳定结合。结论附子-丹参可能通过AKT1、TP53、IL-6、TNF、VEGFA等靶点发挥抑制窦房结及周围组织纤维化、调节离子通道、保护心肌、阻止其他疾病对SSS的诱发等机制治疗SSS。

Objective Using network pharmacology and molecular docking techniquesto explore the mechanism of monkshood-salvia miltiorrhiza in the treatment of Sick Sinus Syndrome.Methods Searching and screening the active ingredients and targets of monkshood and salvia miltiorrhiza by TCMSP database;Predicting the therapeutic targets of SSS using DisGeNET,GeneCards,OMIM database,the potential targets of the monkshood-salvia miltiorrhiza drug pair for the treatment of SSS were refined using the VEnn map,and then the PPI network was constructed by String database and Cytoscape 3.7.2 to obtain the key targets by topological analysis.Use Metascape database to annotate GO function and analyze KEGG enrichment of targets.Finally,use AutoDock software to perform Macromolecular docking between key target genes and active ingredients,and use Pymol software to draw docking results.Results A total of 65 active ingredients were mined and 77 targets were associated with the improvement of SSS.The important targets for the treatment of SSS involved AKT1,TP53,IL-6,TNF,VEGFA,etc.They mainly acted on lipid and atherosclerotic pathways,relaxin signaling pathway,calcium signaling pathway,cAMP signaling pathway,NF-κB signaling pathway,apoptosis,adipocyte lipolysis and other signaling pathways.Molecular docking results showed stable binding between core components and core targets.Conclusion monkshood-salvia miltiorrhiza may exert mechanisms through AKT1,TPT53,IL-6,TNF,VEGFA and other targets to inhibit fibrosis in the sinoatrial node and surrounding tissues,regulate ion channels,protect the myocardium,and prevent the triggering of SSS by other diseases for the treatment of SSS.