基于网络药理学和分子对接探究参芎葡萄糖注射液抗心肌缺血再灌注损伤的作用机制  

Mechanism of Shenxiong Glucose Injection against myocardial ischemia-reperfusion injury based on network pharmacology and molecular docking

作　　者：李长健 马贤鹏 聂红[1] LI Chang-jian;MA Xian-peng;NIE Hong(College of Pharmacy,Jinan University,Guangzhou 510632,China;Guizhou Jingfeng Injection Co.,Ltd.,Guiyang 550018,China)

机构地区：[1]暨南大学药学院,广东广州510632 [2]贵州景峰注射剂有限公司,贵州贵阳550018

出　　处：《中国中药杂志》2022年第10期2759-2766,共8页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(81673634)。

摘　　要：基于网络药理学和分子对接预测参芎葡萄糖注射液(Shenxiong Glucose Injection,SGI)的主要活性成分丹参素和川芎嗪抗心肌缺血再灌注损伤(myocardial ischemia-reperfusion injury,MIRI)的作用机制。通过中药系统药理学数据库与分析平台、人类基因组注释数据库、人类孟德尔遗传数据库获取化合物和疾病相关靶点,筛选出两者交集基因;利用Cytoscape软件构建“药物-成分-疾病-靶点”网络,STRING平台进行蛋白相互作用分析;应用R软件进行基因本体(Gene Ontology,GO)功能和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析;AutoDock Vina软件对活性成分与核心靶点进行分子对接。结果显示,丹参素和川芎嗪抗MIRI的潜在作用靶点共15个,涉及环氧合酶途径、胞外基质结合、抗氧化活性等过程,且与血小板活化、脂肪细胞脂解的调控等通路密切相关。丹参素、川芎嗪与核心靶点前列腺素内过氧化物合酶2、血管内皮生长因子A、乙酰胆碱酯酶均能形成结合能较低的稳定构象。综上所述,SGI可能通过环氧合酶途径等生物过程治疗MIRI,并涉及胞外基质结合、抗氧化活性等分子功能,且与血小板活化、脂肪细胞脂解的调控等信号通路密切相关。充分体现了SGI多成分、多靶点、多通路、协同作用的特点,为进一步深入阐明SGI抗MIRI的作用机制提供理论参考。Based on network pharmacology and molecular docking,the mechanism of danshensu and tetramethylpyrazine,the main active components of Shenxiong Glucose Injection(SGI),against myocardial ischemia-reperfusion injury(MIRI)was explored.Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),GeneCards,and Online Mendelian Inheri-tance in Man(OMIM)were used to search the targets of the active components and the disease,and the common targets were screened.The"drug-component-disease-target"network was constructed by Cytoscape,and the protein-protein interaction network was established by STRING,followed by Gene Ontology(GO)term and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment by R software.AutoDock Vina was employed for the molecular docking between active components and core targets.A total of 15 potential targets of danshensu and tetramethylpyrazine against MIRI were screened out,involving the major GO terms of cyclooxyge-nase pathway,extracellular matrix binding,and antioxidant activity,and the main pathways of platelet activation and regulation of lipolysis in adipocytes.Danshensu and tetramethylpyrazine can form stable conformations with core targets prostaglandin G/H synthase 2(PTGS2),vascular endothelial growth factor A(VEGFA),and acetylcholinesterase(ACHE)with low binding energy.This study reflects the multi-component,multi-target,multi-pathway,and synergistic action characteristics of SGI,which provides a theoretical re-ference for further clarifying the anti-MIRI mechanism of SGI.

关 键 词：心肌缺血再灌注损伤 参芎葡萄糖注射液 丹参素 川芎嗪 网络药理学 分子对接 

分 类 号：R285[医药卫生—中药学]