基于网络药理学和分子对接探讨芪参益心颗粒治疗射血分数保留型心力衰竭的作用机制  

Effects and mechanism of Ginseng Yixin granules(QSYXG)for heart failure with preserved ejection fraction based on the network pharmacology and molecular docking strategy

作　　者：陈玉林 蒋虎刚 王新强 刘凯 李应东 安涛[4] 赵信科 CHEN Yulin;JIANG Hugang;WANG Xinqiang;LIU Kai;LI Yingdong;AN Tao;ZHAO Xinke(College of Integrated Traditional Chinese and Western Medicine,Gansu University of Traditional Chinese Medicine,Lanzhou 730000,Gansu,China;The Third Affiliated Hospital of Gansu University of Traditional Chinese Medicine,Baiyin 730900,Gansu,China;Key Laboratory of Prevention and Treatment of Chronic Diseases,Gansu Province,Lanzhou 730000,Gansu,China;Heart Failure Center,Fuwai Hospital,National Cardiovascular Center of Chinese Academy of Medical Sciences,Peking Union Medical College,Beijing 100037,China)

机构地区：[1]甘肃中医药大学中西医结合学院,甘肃兰州730000 [2]甘肃中医药大学第三附属医院,甘肃白银730900 [3]甘肃省中医药防治慢性疾病重点实验室,甘肃兰州730000 [4]北京协和医学院中国医学科学院国家心血管病中心阜外医院心力衰竭中心,北京100037

出　　处：《中国临床药理学与治疗学》2023年第10期1081-1092,共12页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：中医药传承与创新“百千万”人才工程(岐黄工程)青年岐黄学者基金资助项目;2021年度“双一流”科研重点项目(GSSYLXM-05-ZXYJH-5);甘肃省中医药防治重大疾病科研课题项目(GZKZD-2018-02);甘肃省中医药研究中心专项开放课题(zyzx-2020-zx6、zx9);白银市科技计划项目(2022-2-50Y);甘肃中医药大学第三附属医院院内课题(2022YK-11)。

摘　　要：目的:基于网络药理学和药理学实验揭示芪参益心颗粒治疗射血分数保留型心力衰竭(heart failure with preserved ejection fraction,HFpEF)的生物活性化合物和分子机制。方法:通过TCMSP数据库收集芪参益心颗粒有效化学成分信息;DisGeNET、GeneCards、OMIM数据库获取HFpEF相关靶点;Metascape对芪参益心颗粒及HFpEF交集靶点进行GO及KEGG富集分析。利用STRING数据库PPI网络的构建与分析;Cytoscape 3.7.2软件构建网络图;对主要活性成分与核心靶点用AutoDock Vina软件分子对接,用pymol对结果进行可视化分析。用CCK8法检测各组细胞存活率,对结果分析出的重要蛋白进行蛋白免疫印迹法(Western blot)验证。结果:共得到芪参益心颗粒66个成分及对应240个靶点,HFpEF对应靶点1931个,芪参益心颗粒与HFpEF二者交集靶点127个,主要活性成分为槲皮素、山柰酚、β-谷甾醇等;TNF、AKT1、IL-6、P53、JUN为核心靶点,分子对接显示关键成分与核心靶点对接良好;主要涉及了基因表达正向调节、凋亡调控、细胞增殖和衰老、缺氧反应、炎症反应等,PI3K-Akt、AGE-RAG、MAPK、TNF、IL-17为主要相关信号通路。蛋白免疫印迹法(Western blot)结果:与空白组比较,阴性对照组TNF、AKT1、IL-6、P53及JUN蛋白表达无统计学差异(P>0.05);与阴性对照组相比,模型组TNF、IL-6、P53及JUN蛋白表达均上调(P<0.05),AKT蛋白表达下调(P<0.05);与模型组比较,芪参益心颗粒低、中、高剂量组TNF、IL-6、P53及JUN蛋白表达均下调(P<0.05),AKT蛋白表达上调(P<0.05)。结论:芪参益心颗粒可能是通过作用于TNF、AKT1、IL-6、P53、JUN等靶点,通过参与调节基因表达细胞凋亡和增殖、缺氧反应、炎症反应等作用,从而治疗HFpEF。AIM:To study the mechanism of Ginseng Yixin granules(QSYXG)in treating ejection fraction preserved heart failure(HFpEF)based on network pharmacology.METHODS:Effective chemical composition information of QSYXG particles was collected through TCMSP database;DisGeNET,GeneCards,OMIM database for obtaining HFpEF related targets;Metascape GO and KEGG enrichment analysis of the intersection targets of HFpEF;STRING Construction and analysis of the database PPI network;Cytoscape3.7.2 Software construction network diagram;Docking of the major active components to the core target with the AutoDock Vina software molecules,the results were visualized and analyzed with pymol.RESULTS:A total of 66 components and corresponding targets were obtained,HFpEF corresponds to 1931 targets,The intersection of 127 targets,the main active ingredients are quercetin,kaempferol,β-sitosterol,etc.;TNF,AKT1,IL-6,P53 and JUN as the core targets,Good docking of the key components with the core targets;Mainly involving the positive regulation of gene expression,signal transduction,negative regulation of apoptotic process,positive regulation of cell proliferation and senescence,hypoxia response,negative regulation of gene expression,inflammatory response and so on,PI3K-Akt,AGE-RAG,MAPK,TNF,IL-17,and HIF-1 are the main associated signaling pathways.CONCLUSION:QSYXG may treat HFpEF by activating targets of TNF,AKT1,IL-6,P53,JUN,and regulating apoptotic process,cell proliferation,hypoxia response,and inflammatory response.

关 键 词：网络药理学 分子对接 芪参益心颗粒 射血分数保留型心力衰竭 作用机制 信号通路 

分 类 号：R965.2[医药卫生—药理学]