黄芪-水蛭药对调控铁死亡治疗脑缺血再灌注损伤作用机制探析  

Mechanism of"Astragalus-Leech"medicine pair for treatment of cerebral ischemia-reperfusion injury by regulating ferroptosis

作　　者：杨智倩 江杰 刘为 王晶菊 杨鸿[1,2] YANG Zhiqian;JIANG Jie;LIU Wei;WANG Jingju;YANG Hong(Medical Experimental Center,China Academy of Chinese Medical Sciences,Beijing 100700,China;Beijing Key Laboratory of Traditional Chinese Medicine for Prevention and Treatment of Major Diseases,Beijing 100700,China)

机构地区：[1]中国中医科学院医学实验中心,北京100700 [2]北京市中医药防治重大疾病基础研究重点实验室,北京100700

出　　处：《中国药师》2024年第8期1273-1285,共13页China Pharmacist

基　　金：中央级公益性科研院所基本科研业务费专项资金资助(ZZ2018017)。

摘　　要：目的“黄芪-水蛭”药对可以减轻脑缺血再灌注损伤(CIRI),但其作用机制尚未明确。铁死亡是CIRI的新靶点,本文利用网络药理学方法探究“黄芪-水蛭”药对通过调控铁死亡治疗CIRI的作用机制。方法通过检索PubChem、SwissTargetPrediction、Batman-TCM、UniProt、TCMSP等数据库分别获得黄芪、水蛭的有效活性成分和作用靶点;检索GeneCards数据库收集CIRI相关靶点;利用Venny在线工具获得“黄芪-水蛭”药对活性成分和CIRI的共同作用靶点。通过Cytoscape软件得出“黄芪-水蛭”药对活性成分、疾病及预测靶点之间相互关系的网络,将蛋白互作网络图进行可视化处理,并使用CytoHubba插件计算得出核心靶点。应用R语言软件对“黄芪-水蛭”治疗CIRI的靶点进行GO分析和KEGG分析。利用FerrDb数据库,获取调控铁死亡的相关基因,将“黄芪-水蛭”药对活性成分、CIRI、铁死亡三者之间的公共基因进行分析,探究其关系并作出预测。使用AutoDockTools 1.5.7等软件对药对活性成分与关键靶点进行分子对接验证。结果通过数据库检索共收集到“黄芪-水蛭”药对有效活性成分28个、预测得到药对基因靶点680个,CIRI相关靶点1513个,药对-疾病的共同靶点253个,铁死亡相关靶点259个,进行相关预测得到包括PIK3CA、RELA、MAPK1、MAPK8、PTGS2、STAT3、SRC、NOS2等28个“黄芪-水蛭”药对调控铁死亡干预CIRI的可能作用靶点,及包括PI3K-Akt、Ras、TNF、MAPK、HIF-1信号传导途径在内的279条信号通路。分子对接显示,药对关键成分和核心靶点之间有相互作用关系,“黄芪-水蛭”药对可能通过调控铁死亡干预CIRI的发生发展而发挥治疗作用。结论利用网络药理学方法,分析挖掘出“黄芪-水蛭”药对活性成分通过调控铁死亡抗CIRI的潜在靶点及其相关通路,提示“黄芪-水蛭”可能通过氧化应激和抗炎途径调控铁死亡途径发挥其抗CIRI的�Objective"Astragalus-Leech"medicine pair can reduce cerebral ischemiareperfusion injury(CIRI),but its mechanism of action is not yet clear.Ferroptosis is a new target of CIRI.In this paper,the mechanism of the"Astragalus-Leech"medicine pair on regulating ferroptosis in the treatment of CIRI was investigated using the network pharmacology approach.Methods The active ingredients and targets of Astragalus-Leech were obtained by searching databases,such as PubChem,SwissTargetPrediction,Batman-TCM,UniProt,TCMSP and other databases,respectively;the CIRI-related targets were collected by searching GeneCards database;the Venny online tool was used to obtain the common targets of"Astragalus-Leech"medicine pairs for active ingredients and CIRI.Cytoscape software was used to construct a network of interrelationships between the active ingredients,disease and predicted targets of the"Astragalus-Leech"medicine pair,the protein interaction network was visualized,and CytoHubba plug-in was used to calculate the core targets.The GO analysis and KEGG analysis of the targets of"Astragalus-Leech"in the treatment of CIRI were performed using R language software.Using FerrDb database,the genes related to the regulation of ferroptosis were obtained,and the common genes among the active ingredients,CIRI and ferroptosis in the"Astragalus-Leech"medicine pair were analyzed to investigate their relationship and make predictions.AutoDockTools 1.5.7 and other softwares were used to verify the molecular docking between the active ingredients and key targets.Results Through searching the databases,28 active ingredients of"Astragalus-Leech"medicine pair,680 predicted gene targets of the drug pair,1513 targets related to CIRI,253 common targets of drug pair-disease,259 targets related to ferroptosis were obtained.28 potential targets,including PIK3CA,RELA,MAPK1,MAPK8,PTGS2,STAT3,SRC,NOS2,etc.on the regulation of ferroptosis and intervention in CIRI,and 279 signaling pathways including PI3K-Akt,Ras,TNF,MAPK,and HIF-1 were obtained through related

关 键 词：黄芪 水蛭 网络药理学 分子对接 脑缺血再灌注损伤 铁死亡 氧化应激 炎症 作用机制 

分 类 号：R285[医药卫生—中药学]