基于网络药理学及分子对接技术探讨真武汤治疗射血分数保留心力衰竭的作用机制  

Potential mechanism of Zhenwu Decoction acting on heart failure with preserved ejection fraction based on Network pharmacology and molecular docking technology

作　　者：和振杰 时晓迟[2] 赵英强[2] HE Zhenjie;SHI Xiaochi;ZHAO Yingqiang(Graduate School of Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China)

机构地区：[1]天津中医药大学研究生院,301617 [2]天津中医药大学第二附属医院心内科

出　　处：《环球中医药》2024年第11期2234-2249,共16页Global Traditional Chinese Medicine

摘　　要：目的基于网络药理学及分子对接技术探讨真武汤治疗射血分数保留心力衰竭(heart failure with preserved ejection fraction,HFpEF)的作用机制。方法利用TCMSP平台筛选真武汤候选活性成分,Swisstargetprediction平台预测化合物靶点,NCBI Gene、OMIM、DisGenet、GenCards、PharmgKB数据库中检索HFpEF疾病靶点;取交集靶点,利用String数据库和Cytoscape 3.9.1软件进行蛋白质—蛋白质相互作用(protein-protein interaction,PPI)和拓扑分析,获得关键活性成分和枢纽靶基因;Metescape平台对共同靶点进行基因本体(Gene ontology,GO)功能和京都基因与基因组百科全书(Kyoto Encyclopedia of Genesand Genomes,KEGG)通路富集分析。以真武汤的活性成分为配体,以其枢纽靶点为受体,进行分子对接可视化。结果真武汤有效成分和HFpEF筛选出362个共同作用靶点,Cytoscape 3.9.1软件筛选出包括白细胞介素-6、雌激素受体1、肿瘤坏死因子和基质金属蛋白酶9等10个枢纽靶点,德尔妥因、去氧穿心莲内酯和新南五味子酸B等10个核心化合物。GO与KEGG富集分析分别得到1393、171个条目(P<0.01)。分子对接结果显示核心化合物和枢纽靶点具有较好的亲和力。结论真武汤方中的核心有效成分作用于多靶点,可能通过调节磷脂酰肌醇3激酶/蛋白激酶B、糖尿病并发症中的晚期糖基化终末产物-糖基化终产物受体、大鼠肉瘤、大鼠肉瘤同源蛋白1以及丝裂原活化蛋白激酶等多信号通路发挥作用,干预HFpEF的发展进程,为后续研究提供参考依据。Objective To explore the mechanism of Zhenwu Decoction in treating heart failure with preserved ejection fraction(HFpEF)based on network pharmacology and molecular docking.Methods TCMSP platform was used to screen the candidate active ingredients of Zhenwu Decoction,compound targets were predicted on the Swisstargetprediction platform,and disease targets of HFpEF were searched in databases such as NCBI Gene,OMIM,DisGenet,GenCards,and PharmgKB.Intersectional targets were taken,and protein-protein interaction and topological analysis were performed using String database and Cytoscape 3.9.1 software to obtain key active ingredients and hub target genes.Gene ontology(GO)and Kyoto Encyclopedia of Genesand Genomes(KEGG)pathway enrichment analysis were conducted on the Metescape platform for common targets.Molecular docking visualization was performed with active ingredients of Zhenwu Decoction as ligands and hub targets as receptors.Results A total of 362 common action targets were identified between Zhenwu Decoction and HFpEF,and 10 hub targets including IL-6,ESR1,TNF,and MMP9 were selected by Cytoscape 3.9.1 software.The GO function and KEGG pathway enrichment analysis yielded 1393 and 171 items,respectively(P<0.01).Molecular docking results showed that the core compounds had good affinity with hub targets.Conclusion The core effective components in Zhenwu Decoction act on multiple targets,possibly regulating multiple signaling pathways such as phosphatidylinositol 3-kinase/protein kinase B,advanced glycation end products-receptor for advanced glycation endproducts,rat sarcoma(Ras),Ras-homologous protein 1,and mitogen-activated protein kinase to intervene in the development process of HFpEF.This provides a reference for further research.

关 键 词：真武汤 射血分数保留心力衰竭 网络药理学 有效成分 通路分析 分子对接 

分 类 号：R259[医药卫生—中西医结合]