目的:通过网络药理学及分子对接技术探讨苦参在防治心肌缺血再灌注损伤(Myocardial Ischemia Reperfusion Injury,MIRI)中的作用机制.方法:借助中药系统药理学数据库与分析平台(TCMSP)筛选苦参的有效成分,通过GeneCards数据库、OMIM数据库检索MIRI相关疾病靶点.制作苦参成分靶点与MIRI疾病靶点之间的韦恩图,获取交集靶点.运用CytoScape 3.8.2软件建立"苦参-成分-靶点-MIRI"网络,导入STRING数据库获取靶点蛋白质-蛋白质相互作用网络,选出核心靶点,利用DAVID数据库进行基因本体论(GO)生物进程及京都基因与基因组百科全书(KEGG)通路富集分析,使用AutoDock软件对核心靶点与有效成分进行分子对接,选择最佳的结合靶点进行可视化.结果:从苦参中筛选出23个有效成分,作用于MIRI的交集靶点有116个.网络药理学分析显示苦参中槲皮素、木犀草素、刺芒柄花素等有效成分可能通过丝氨酸/苏氨酸蛋白激酶 1(Akt Serine/Threonine Kinase 1,AKT1)、白细胞介素(Interleukin,IL)-6、肿瘤坏死因子(Tumor Necrosis Factor,TNF)等关键基因调控晚期糖基化终末产物(Advanced Glycation End-product,AGE)-晚期糖基化终末产物受体(Receptor for Advanced Glycation End Products,RAGE)信号通路、流体剪切应力与动脉粥样硬化相关通路、IL-17信号通路、TNF信号通路、缺氧诱导因子1(Hypoxia Inducible Factor-1,HIF-1)信号通路、凋亡信号通路等通路发挥防治MIRI的作用.结论:苦参可能通过多成分、多靶点和多途径整合调节防治MIRI.
Exploration on the mechanism of Kushen in preventing myocardial ischemia reperfusion injury based on network pharmacology and molecular docking
Objective:To explore the mechanism of Kushen(Radix Sophorae Fiavescentis)in preventing myocardial ischemia reperfusion injury by network pharmacology and molecular docking.Methods:The effective ingredients of Kushen(Radix Sophorae Fiavescentis)were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and MIRI related disease targets were searched by GeneCards database and OMIM database.The Venn diagram of the target of Kushen(Radix Sophorae Fiavescentis)ingredients and the targets of MIRI disease was made to obtain the intersection target.The"Kushen(Radix Sophorae Fiavescentis)-ingredient-target-MIRI"network was established by CytoScape 3.8.2 software and was imported into STRING database to obtain target PPI network,core target was selected,and GO biological process and KEGG pathway enrichment analyses were carried out using DAVID database.AutoDock software was used to perform molecular docking between the core target and the active ingredients,and the best binding target was selected for visualization.Results:A total of 23 active ingredients were selected from Kushen(Radix Sophorae Fiavescentis),and 116 intersection targets of myocardial ischemia reperfusion injury were detected.Network pharmacological analysis showed that effective ingredients of quercetin,luteolin and onononetin in Kushen(Radix Sophorae Fiavescentis)may regulate AGE-RAGE signaling pathway,fluid shear stress and atherosclerotic pathway,IL-17 signaling pathway,TNF signaling pathway,HIF-1 signaling pathway and apoptosis signaling pathway through key genes such as AKT1,IL-6 and TNF to play a role in preventing and treating MIRI.Conclusion:Kushen(Radix Sophorae Fiavescentis)may prevent and treat MIRI through multi-ingredient,multi-target and multi-pathway integration.
万方数据
维普
