基于网络药理学探讨参蛭通心胶囊核心药对人参-水蛭治疗扩张型心肌病的作用机制  

Study on the Mechanism of Core Drug Pair Ginseng-Leech of Shenzhi Tongxin Capsule in the Treatment of Dilated Cardiomyopathy Based on Network Pharmacology

作　　者：齐璐瑶 邢基祥 范吉林 侯信铮 陈昭 张世亮[2] QI Luyao;XING Jixiang;FAN Jilin;HOU Xinzheng;CHEN Zhao;ZHANG Shiliang(Shandong University of Traditional Chinese Medicine,Jinan 250014,China;Affiliated Hospital of Shandong University of Traditional Chinese Medicine,Jinan 250014,China)

机构地区：[1]山东中医药大学,山东济南250014 [2]山东中医药大学附属医院,山东济南250014

出　　处：《西部中医药》2024年第3期44-51,共8页Western Journal of Traditional Chinese Medicine

基　　金：国家科技重大专项重大新药创制项目(2017ZX09301003)。

摘　　要：目的:基于网络药理学方法探究参蛭通心胶囊核心药对人参-水蛭治疗扩张型心肌病(dilated cardiomyopathy,DCM)的作用机制。方法:通过中药系统药理学数据库与分析平台(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)、BATMAN-TCM数据库获取人参-水蛭药对的活性成分及潜在靶点并导入UniProt数据库对所得基因进行标准化处理;运用人类基因数据库(the human gene database,GeneCards)获取DCM已知靶点;通过绘制韦恩图得到药物与疾病的交集靶点,将药物活性成分及药物-疾病共同靶点等数据导入Cytoscape 3.7.2软件,构建药物-成分-疾病-靶点网络;运用STRING数据库构建蛋白-蛋白互作网络(protein-protein interactions,PPI)并筛选出核心靶点;将核心靶基因导入基因功能注释数据库(the database for annotation visualization and integrated discovery,DAVID)平台对所得交集靶点进行基因本体(gene ontology,GO)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,同时利用OmicShare进行数据的可视化分析。结果:经筛选共获得人参-水蛭药对有效成分35个,药物-疾病交集靶点184个,涉及的核心靶点主要有胰岛素、白蛋白、肿瘤坏死因子、内皮一氧化氮合成酶、过氧化物酶体增殖物激活受体、白细胞介素1β等。人参-水蛭的有效成分通过对细胞膜、细胞外间隙、电压门控钙通道复合体等部位的作用、一氧化氮生物合成过程的正调控、细胞间信号传递、对凋亡过程的负调控等过程和CAMP信号通路等在内的多个信号通路协同作用治疗DCM。结论:参蛭通心胶囊的核心药对人参-水蛭可以通过参与调控多成分、多靶点、多通路治疗DCM。Objective:To explore the mechanism of the core drug pair ginseng and leech in Shenzhi Tongxin Capsule in the treatment of dilated cardiomyopathy(DCM)based on network pharmacology.Methods:The active ingredients and potential targets of drug pair ginseng and leech were gained through TCMSP and BATMAN-TCM databases,to perform the standardized processing after imported into the Uniprot database.The known targets of DCM were obtained using the GeneCards database.The intersection targets of drugs and diseases were obtained by drawing a Venn diagram.The data on active ingredients of the drugs and drug-disease common targets was introduced into Cytoscape 3.7.2 software to construct a drug-component-disease-target network.Protein-protein interaction(PPI)network was constructed and core targets were screened out using the STRING database.DAVID database platform was used to perform GO function and KEGG pathway enrichment analysis of the obtained intersection targets,at the same time,Omicshare was applied for visualization analysis of the data.Results:After screening,a total of 35 effective ingredients were obtained,corresponding to 184 targets.The core targets involved mainly included insulin(INS),albumin(ALB),tumor necrosis factor(TNF),endothelial nitric oxide synthase(NOS3),peroxisome proliferator activated receptor(PPARG),interleukin-1β,etc.The active ingredients of ginseng-leech could treat DCM through synergistic effects of multiple signaling pathways,including cell membrane,extracellular space,voltage-gated calcium channel complex,positive regulation of nitric oxide biosynthesis process,intercellular signal transduction,negative regulation of apoptosis process,and CAMP signaling pathway.Conclusion:The core drug pair ginseng-leech of Shenzhi Tongxin capsule could treat DCM by participating in the regulation of multiple ingredients,multiple targets and multiple pathways.

关 键 词：扩张型心肌病 网络药理学 参蛭通心胶囊 人参-水蛭 作用机制 

分 类 号：R256.21[医药卫生—中医内科学]