基于网络药理学探讨铁筷子醇提物防治心肌梗死的作用及机制  

Effects and mechanism of Tiekuaizi alcohol extract in the prevention and treatment of myocardial infarction based on network pharmacology

作　　者：徐婷 陈铭 王延 伍沙沙 刘晓龙 钱海兵 XU Ting;CHEN Ming;WANG Yan;WU Sha-sha;LIU Xiao-long;QIAN Hai-bing(Guizhou University of Traditional Chinese Medicine,Guizhou Guiyang 550025,China;Research Center for Effectiveness Consistency of Genuine Regional Materia Medica in Guizhou Province,Guizhou Guiyang 520025,China;Foshan Traditional Chinese Medicine Hospital,Guangdong Foshan 528000,China;Department of Medicine,Changde Vocational and Technical College,Hunan Changde 415000,China)

机构地区：[1]贵州中医药大学,贵州贵阳550025 [2]贵州省道地药材性效用一致性研究中心,贵州贵阳550025 [3]佛山市中医院,广东佛山528000 [4]常德职业技术学院医学系,湖南常德415000

出　　处：《中国医院药学杂志》2022年第19期2014-2023,共10页Chinese Journal of Hospital Pharmacy

基　　金：国家自然基金项目(编号:81760773);贵州省优秀科技教育人才省长专项资金项目[编号:黔省专合字(2012)167号]。

摘　　要：目的:探讨铁筷子醇提物(TKZC)防治心肌梗死(myocardial infarction,MI)的作用及机制,为进一步探究TKZC防治MI的有效成分及作用机制提供研究基础。方法:通过查找文献获取TKZC的主要化学成分及其可能作用靶点,根据2个ADME筛选中药活性组分;通过Genecards、OMIM、TTD、DRUGBANK数据库获取疾病主要靶点,后续进行生物过程及通路的信息分析。TKZC干预动脉粥样硬化后急性心肌梗死大鼠的动物实验,采用PCR和Western blot检测心肌组织IκB-α、NF-κBp65、NF-κBp50 mRNA和蛋白的表达,进行相关作用靶点的验证。结果:TKZC防治MI的核心活性成分为丁香酸、异嗪皮啶-7-O-β-D-葡萄糖苷、异嗪皮啶、东莨菪内酯;核心靶点有PPARG、MAPK14、AKT1、F2、SRC;防治MI的生物学通路主要作用与MAPK信号通路,糖尿病并发症中的AGE-RAGE信号通路,流体剪切应力与动脉粥样硬化有关;TKZC可以下调IκB-α、NF-κBp65和NF-κBp50 mRNA和蛋白的表达,抑制NF-κB信号通路的激活起到对缺血心肌的保护作用。结论:网络药理学预测丁香酸为TKZC防治MI的主要成分,其防治MI的作用机制与动脉粥样硬化和NF-κB信号通路有关,作用靶点可能与IκB-α、NF-κBp65和NF-κBp50有关。OBJECTIVE To investigate the effects and mechanism of Tiekuaizi alcohol extract(TKZC)in the prevention and treatment of myocardial infarction,and to provide research basis for further exploration of the active components and mechanism of TKZC.METHODS First of all,the components and their possible action targets of TKZC were obtained by document retrieval,and the active components were screened through two ADME.Secondly,the main disease targets were obtained through Genecards,OMIM,TTD and DRUGBANK databases.Subsequently,the biological processes and pathways were analyzed by information network.Finally,an animal experiment was conducted to investigate the effects of TKZC on acute myocardial infarction after atherosclerosis in rats.The mRNA and protein expression of IκB-α,NF-κBp65 and NF-κBp50 in myocardial tissue were detected by PCR and Western blot,and the relevant targets and mechanism of action were verified.RESULTS The results showed that the core active components of TKZC in the prevention and treatment of myocardial infarction were syringic acid,calycanthoside,isofraxidin and scopoletin.The core targets were PPARG,MAPK14,AKT1,F2 and SRC.Biological pathways in the prevention and treatment of myocardial infarction were mainly related to MAPK signaling pathway,AGE-RAGE signaling pathway in diabetic complications,fluid shear stress and atherosclerosis.TKZC could down-regulate the mRNA and protein expression of IκB-α,NF-κBp65 and NF-κBp50,inhibit the activation of NF-κB signaling pathway and play a protective role in ischemic myocardium.CONCLUSION Network pharmacology predicted that syringic acid is the main component of TKZC in the prevention and treatment of myocardial infarction,and the mechanism of its prevention and treatment of myocardial infarction is related to atherosclerosis and NF-κB signaling pathway,and the targets of its action might be related to IκB-α,NF-κBp65 and NF-κBp50.

关 键 词：铁筷子醇提物 心肌梗死 网络药理学 NF-κ B信号通路 

分 类 号：R966[医药卫生—药理学]