基于网络药理学和分子对接技术探讨甘松对心房颤动的分子作用机制  

The molecular action mechanism of Gansong on atrial fibrillation based on network pharmacology and molecular docking technology

作　　者：姜悦 宫丽鸿[2] JIANG Yue

机构地区：[1]辽宁中医药大学研究生学院,辽宁沈阳110847 [2]辽宁中医药大学附属医院,辽宁沈阳110000

出　　处：《中医临床研究》2024年第11期80-88,共9页Clinical Journal Of Chinese Medicine

基　　金：辽宁省特聘教授项目(辽教函[2018]35号)(21601A10881);辽宁省应用基础研究计划项目:中药复方治疗痰浊血瘀型房颤的疗效及机制研究(2022JH2/101300086)。

摘　　要：目的:基于网络药理学和分子对接技术探讨甘松治疗心房颤动的作用靶点及通路,探讨甘松治疗心房颤动的作用机制。方法:应用中药系统药理学数据库与分析平台(TCMSP)检索甘松的活性成分,预测其作用靶点。检索DrugBank、GeneCards、OMIM和DisGeNET数据库,收集心房颤动治疗相关靶点,并得到甘松与心房颤动交集靶点。使用Cytoscape 3.7.2软件构建药物-活性成分-潜在作用靶点网络,得到甘松治疗心房颤动的关键成分。运用STRING数据库获取交集靶点的蛋白质-蛋白质相互作用网络,然后进行可视化分析,并筛选关键靶点。应用Metascape数据库进行基因本体论(GO)功能分析和京都基因与基因组百科全书(KEGG)通路富集分析。最后使用PyMOL、AutoDock4.2.6和AutoDockTools1.5.7软件将关键成分与关键靶点进行分子对接验证。结果:甘松治疗心房颤动的关键成分有熊果酸、隐丹参酮、金合欢素等。通过蛋白质-蛋白质相互作用网络筛选获得半胱氨酸天冬氨酸蛋白酶-3、白细胞介素(Interleukin,IL)-6、肿瘤坏死因子(Tumor Necrosis Factor,TNF)、细胞肿瘤抗原p53、血管内皮生长因子A(Vascular Endothelial Growth Factor A,VEGFA)等为重要靶点,KEGG富集分析结果提示甘松治疗心房颤动主要通过癌症通路、磷脂酰肌醇3激酶(Phosphatidylinositol 3-kinase,PI3K)-蛋白激酶B(Akt)信号通路、糖尿病并发症中的晚期糖基化终末产物-晚期糖基化终末产物受体信号通路、TNF信号通路以及IL-17信号通路等通路发挥作用。分子对接表明,甘松的主要活性成分能够很好地与关键核心靶点结合。结论:甘松基于多成分、多靶点、多通路治疗心房颤动,为后续开展实验研究进一步阐述其作用机制提供了科学依据。Objective:Based on the network pharmacology and molecular docking technology,the action targets and pathways Oof Gansong(Rhizoma Nardostachyos)in the treatment of atrial fibrillation was explored to discuss the action mechanism of Gansong on atrial fibrillation.Methods:TCMSP database was used to search the active constituents of Gansong,and their action targets were predicted.DrugBank,GeneCards,OMIM and DisGeNET databases were used to collect targets related to the treatment of atrial fibrillation,then the intersection targets of Gansong and atrial fibrillation was obtained.Cytoscape 3.7.2 software was used to construct a network of drug-active ingredients-potential action targets,so as to obtain the key ingredients of Gansong on atrial fibrillation.STRING database was used to obtain the protein-protein interaction(PPI)network of intersecting targets.The PPI network was visualized and analyzed to screen key targets.The Metascape database was used for gene ontology(GO)functional enrichment analysis and Kyoto genomic and genomic encyclopedia(KEGG)pathway enrichment analysis.Finally,PyMOL,AutoDock 4.2.6 and AutoDockTools 1.5.7 were used to verify the molecular docking between key components and key targets.Results:The key targets of Gansong on atrial fibrillation include ursolic acid,cryptotanshinone and acacetin,etc.Important action targets such as caspase3,interleukin(IL-6),tumor necrosis factor(TNF),celltumor antigen p53 and vascular endothelial growth factor A were obtained through PPI network screening.The results of KEGG enrichment analysis showed that Gansong played a role in the treatment of atrial fibrillation mainly through cancer pathways,PI3K-Akt signaling pathway,AGE-RAGE signaling pathway in diabetic complications,TNF signaling pathway and IL-17 signaling pathway.The molecular docking showed that the main active components of Gansong can combine well with key core targets.Conclusion:Gansong is a multi-component,multi-target and multi-pathway method on atrial fibrillation,which provides a scientific bas

关 键 词：甘松 心房颤动 网络药理学 分子对接 作用机制 

分 类 号：R256.2[医药卫生—中医内科学]