基于网络药理学的大果木姜子油治疗心力衰竭作用机制研究  

Study on the Mechanism of oil of Cinnamomum Migao H.W.Li in the Treatment of Heart Failure Based on Network Pharmacology

作　　者：陈向云 汤小芳 李军 黄朝霞 杨桃梅 杨长福 李尧锋 Chen Xiangyun;Tang Xiaofang;Li Jun;Huang Zhaoxia;Yang Taomei;Yang Changfu;Li Yaofeng(School of Basic Medicine,Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China;Resource Institute for Chinese&Ethnic Materia Medica,Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China)

机构地区：[1]贵州中医药大学基础医学院,贵州贵阳550025 [2]贵州中医药大学中药民族药资源研究院,贵州贵阳550025

出　　处：《亚太传统医药》2022年第1期143-151,共9页Asia-Pacific Traditional Medicine

基　　金：国家自然科学基金地区项目(81960864);贵州省普通高等学校科技拔尖人才支持计划(黔教合KY字[2016]075);贵州省科学技术基金(黔科合基础[2016]1401);贵阳中医学院学术新苗培养及创新探索专项(黔科合平台人才[2017]5735号-06)。

摘　　要：目的:揭示大果木姜子油治疗心力衰竭的作用机制。方法:首先从动物药理学实验验证疗效,采用异丙肾上腺素(ISO)诱导复制心力衰竭大鼠模型,造模成功后应用大果木姜子油治疗4周,监测血流动力学指标,分析血清BNP水平和心肌组织形态学变化;然后基于文献检索和TCMSP数据库获取大果木姜子油活性成分及作用靶点,从CTD和Drugbank数据库筛选心力衰竭的已知治疗靶点,将疾病治疗靶点与大果木姜子油活性成分作用靶点进行Venn分析,运用SYBYL软件进行分子对接验证,运用STRING数据库分析蛋白互作关系,再利用DAVID数据库进行GO分子功能和KEGG通路富集分析。结果:大果木姜子油可显著升高ISO诱导的心衰大鼠LVSP、±dp/dtmax,降低LVEDP和BNP水平,改善心肌组织形态学变化;获得大果木姜子油20个活性成分,其中7个活性成分(沉香螺旋醇、芳樟醇、萜品烯-4-醇等)可能通过调控一个蛋白互作网络治疗心力衰竭,该网络中的靶点有PTGS1、PTGS2、NOS2、NOS3、GSK3B;由蛋白富集分析发现,这些靶点与前列腺素内过氧化物合酶活性和一氧化氮合酶活性有关。结论:大果木姜子油可改善心衰大鼠的血流动力学紊乱及心肌组织形态学变化;其治疗心力衰竭的机制可能与调控前列腺素内过氧化物合酶活性和一氧化氮合酶活性有关。Objective:To explore the mechanism of oil of Cinnamomum migao H.W.Li in the treatment of heart failure,and to provide theoretical reference for the application of oil of Cinnamomum migao H.W.Li.Methods:Firstly,the curative effect of oil of Cinnamomum migao H.W.Li was verified by animal pharmacological experiments.The rat model of heart failure was induced by isoproterenol(ISO).After the model was successfully treated with oil of Cinnamomum migao H.W.Li for 4 weeks,the hemodynamic indexes were monitored,the levels of serum BNP and myocardial histomorphology were analyzed.And then based on the literature search and TCMSP database to obtain the active ingredients and targets of oil of Cinnamomum migao H.W.Li,the known therapeutic targets of heart failure were screened from CTD and Drugbank database,and the target of disease treatment and the active components of ginger seed oil were targeted.Click to perform Venn analysis,SYBYL software for molecular docking verification,and STRING database to analyze protein interaction relationships,and the DAVID database was used to analyze the molecular function of go and the enrichment of KEGG pathway.Results:Oil of Cinnamomum migao H.W.Li can significantly increase LVSP,±dp/dtmax,and decrease the levels of LVEDP and BNP,and improve the morphological changes of myocardial tissue in rats with heart failure induced by ISO.Twenty active components were obtained and seven active components of oil of Cinnamomum migao H.W.Li(resveratrol,linalool,terpene-4-ol,etc.)could treat heart failure by regulating in a protein interaction network,these targets are PTGS1,PTGS2,NOS2,NOS3,GSK3 B.Protein enrichment analysis showed that these targets were related to the activities of peroxidase and nitric oxide in prostaglandin.Conclusion:Animal pharmacology proved that oil of Cinnamomum migao H.W.Li can improve the hemodynamic disorder and myocardial histomorphological changes in rat with heart failure,and the mechanism of treatment of heart failure may be related to the regulation of prostaglandin

关 键 词：大果木姜子油 心力衰竭 网络药理学 分子对接 作用机制 

分 类 号：R285.5[医药卫生—中药学]