防己茯苓汤治疗射血分数保留型心力衰竭的作用机制  

Network Pharmacology and Molecular Docking to Elucidate the PotentialMechanism of Fangji Fuling Tang Against Heart Failure with Preserved Ejectionfraction

作　　者：周健 邵正斌[2,3] 戚先伟 付玉轩 陈虹 徐海娟 汤忠富 李舒 ZHOU Jian;SHAO Zhengbin;QI Xianwei;FU Yuxuan;CHEN Hong;XU Haijuan;TANG Zhongfu;LI Shu(Anhui University of Chinese Medicine,Anhui Hefei 230031,China;The First Affiliated Hospital of Anhui University of Chinese Medicine,Anhui Hefei 230031,China;Institute of Cardiovascular Diseases,Anhui Academy of Traditional Chinese Medicine,Anhui Hefei 230031,China)

机构地区：[1]安徽中医药大学,安徽合肥230038 [2]安徽中医药大学第一附属医院,安徽合肥230031 [3]安徽中医药科学院心血管病研究所,安徽合肥230031

出　　处：《中医药临床杂志》2022年第10期1910-1917,共8页Clinical Journal of Traditional Chinese Medicine

摘　　要：目的:基于网络药理学探讨防己茯苓汤治疗射血分数保留型心力衰竭(HFpEF)的作用机制。方法:通过TCMSP数据库收集防己茯苓汤有效成分信息;在GeneCards、DisGeNET数据库收集HFpEF靶点;利用Metascape平台对防己茯苓汤及HFpEF交集靶点进行GO及KEGG富集分析;利用Cytoscape3.9.1软件构建相关网络图;最终对主要活性成分与核心靶点应用AutoDock Vina软件进行分子对接验证,并使用pymol对结果进行可视化处理。结果:共整理得到防己茯苓汤的128个成分及其对应的227个靶点,HFpEF靶点1377个,二者交集靶点123个,主要活性成分主要为槲皮素、山柰酚、橙皮素、β-谷甾醇、常春藤素;AKT1、IL-6、TNF、TP53、CASP3是筛选出来的核心靶点,分子对接显示关键成分与靶点对接良好;富集分析发现交集靶点主要参与对脂质的反应、对氧气水平的响应、血液循环、细胞群增殖的负调节、调节凋亡信号等生物过程,以及PI3K-Akt信号通路、血脂与动脉粥样硬化通路、HIF-1信号通路、钙离子信号通路、P53信号通路等通路。结论:防己茯苓汤可能是通过作用于AKT1、IL-6、TNF、TP53、CASP3等靶点,通过参与脂质的反应、对氧气水平的响应、血液循环、细胞群增殖的负调节、调节凋亡信号等作用,从而治疗HFpEF。Objective:To investigate the mechanism of action of tetrandria Fuling Decoction for the treatment of heart failure with preserved ejection fraction(HFPEF)based on network pharmacology.Methods:the information of active ingredients of Fangxi Fuling decoction was collected through TCMSP database;HFPEF targets were collected in genecards,disgenet database;Go and KEGG enrichment analyses were performed on the intersection targets of Fangxi Fuling Decoction and HFPEF using the metascape platform;Correlation network plots were constructed using cytoscape3.9.1;The molecular docking validation was finally performed by applying autodock Vina software between the main active ingredient and the core target,and the results were visualized using PyMOL.Results:A total of 128 components and their corresponding 227 targets of fangzhifuling Decoction were collated,1377 targets of HFPEF and 123 targets of intersection between them,and the main active components were mainly quercetin,kaempferol,hesperetinβ-Sitosterol,ivsu;AKT1,IL-6,TNF,TP53,CASP3 were the core targets screened,and molecular docking showed that the key components docked well with the targets;The enrichment analysis found that the intersection targets were mainly involved in biological processes such as response to lipids,response to oxygen level,blood circulation,negative regulation of cell population proliferation,regulation of apoptotic signaling,and PI3K Akt signaling pathway,blood lipid and atherosclerosis pathway,HIF-1 signaling pathway,calcium ion signaling pathway,and p53 signaling pathway.Conclusions:These results suggest that tetrandria Fuling decoction may treat HFPEF by acting on AKT1,IL-6,TNF,TP53 and CASP3 targets,which are involved in lipid response,response to oxygen level,blood circulation,negative regulation of cell population proliferation,and regulation of apoptotic signaling.

关 键 词：防己茯苓汤 射血分数保留型心力衰竭 网络药理学 分子对接 靶点 信号通路 作用机制 

分 类 号：R256.2[医药卫生—中医内科学]