解毒活血方治疗冠心病的网络药理学机制研究  

Study on Mechanism of Removing Toxins to Activate Blood Recipe for Treatment of Coronary Heart Disease Based on Network Pharmacology

作　　者：刘素丽 吴辉[1] 黄庞宁 陈秋岑 LIU Su-Li;WU Hui;HUANG Pang-Ning;CHEN Qiu-Cen(The First Clinical Medical College,Guangzhou University of Chinese Medicine,Guangzhou 510405 Guangdong,China)

机构地区：[1]广州中医药大学第一附属医院,广东广州510405

出　　处：《广州中医药大学学报》2021年第5期985-991,共7页Journal of Guangzhou University of Traditional Chinese Medicine

基　　金：广州中医药大学“高水平大学建设”面上项目(编号:A1-AFD01817Z11054)。

摘　　要：【目的】基于网络药理学技术探讨解毒活血方治疗冠心病的作用机制。【方法】以化合物生物利用度(OB)>30%且类药性(DL)>0.18为标准,通过中药系统药理学分析平台(TCMSP)筛选解毒活血方中的活性成分及其对应靶标,从GeneCards和在线人类孟德尔遗传(OMIM)数据库获取冠心病相关靶标,利用韦恩(Venn)图获得疾病与药物共同作用靶标。借助Cytoscape3.7.2软件构建活性成分-共同作用靶标网络。结合STRING数据库构建共同靶标蛋白互相作用网络,选取邻接节点数量排名前30位的靶标。利用生物学信息学软件(Bioconductor),通过R语言对共同靶标进行基因本体论(GO)功能富集分析及京都基因与基因组百科全书(KEGG)通路分析,结合文献研究筛选出解毒活血方治疗冠心病的关键信号通路。【结果】从解毒活血方中共筛选出143个活性成分及220个对应靶标,从GeneCards和OMIM数据库中筛选出冠心病相关靶标10 717个,药物与疾病共同靶标204个。靶标蛋白互作网络中邻接节点数量排名前30位的靶标包括STAT3、JUN、AKT1、MAPK1、APP等。经GO和KEGG分析,解毒活血方治疗冠心病主要参与细胞因子受体结合、细胞因子活性、四吡咯结合、血红素结合、核受体的活性、G蛋白偶联胺受体活性、氧化还原酶活性、抗氧化活性、类固醇激素受体活性、类固醇结合、肾上腺素能受体活性、儿茶酚胺结合等生理过程及磷脂酰肌醇-3-羟激酶(PI3K)-苏氨酸激酶(Akt)、流体剪切应力与动脉粥样硬化、高级糖化终产物及其受体(AGE-RAGE)、白细胞介素17(IL-17)、低氧诱导因子1(HIF-1)、肿瘤坏死因子(TNF)等生物信号通路。【结论】解毒活血方治疗冠心病的机制主要与调控炎症介质、动脉粥样硬化形成、血栓形成、血管内皮损伤、血管平滑肌收缩、心率等作用有关。PI3K-Akt、AGE-RAGE信号通路在下一步研究中应有所侧重。Objective To explore the mechanism of Removing Toxins to Activate Blood Recipe for the treatment of coronary heart disease by network pharmacology.Methods With the oral bioavailabilit(OB)>30% and drug-like(DL)>0.18 as the standard,the active ingredients and their corresponding targets in Removing Toxins to Activate Blood Recipe were screened out by Traditional Chinese Medicines Systems Pharmacology Platform (TCMSP)database,the coronary heart disease-related targets were obtained from the Gene Cards and Online Mendelian Inheritance in Mon(OMIM)databases,and then the above common targets were achieved by using the Venn diagram.Furthermore,the active ingredients-common targets network was built by using Cytoscape 3.7.2 software,the protein-protein interaction(PPI)network(common target interaction network)was constructed by STRING database to select the top 30 targets according to the number of adjacent nodes,and then the gene ontology(GO)and Kyoto encyclopedia of genes and gnomes(KEGG)enrichment analysis of the common targets were performed using the Bioconductor database and R language software.Results A total of 143 active ingredients and220 corresponding targets from Removing Toxins to Activate Blood Recipe were screened out,10 717 targets related to coronary heart disease were screened out from Gene Cards and OMIM databases,there were 204 common targets for Removing Toxins to Activate Blood Recipe treating coronary heart disease.The top 30 targets according to the number of adjacent nodes in the PPI included STAT3,JUN,AKT1,MAPK1,APP,etc..The GO and KEGG enrichment analysis results on Removing Toxins to Activate Blood Recipe for coronary heart disease showed that it was mainly involved in cytokine receptor binding,cytokine activity,tetrapyrrole binding,heme binding,nuclear receptor activity,G protein-coupled amine receptor activity,oxidoreductase activity,antioxidant activity,steroid hormone receptor activity,steroid binding,adrenergic receptor activity,catecholamine binding and other physiological processes,and

关 键 词：解毒活血方 冠心病 动脉粥样硬化 网络药理学 

分 类 号：R285.5[医药卫生—中药学]