炙甘草汤“异病同治”冠心病心律失常和肺纤维化的网络药理学机制研究  

Study on Network Pharmacological Mechanisms of‘Homotherapy for Heteropathy'of Zhigancao Decoction in Treating Coronary Heart Disease Arrhythmia and Pulmonary Fibrosis

作　　者：于海睿 万来平 邓绮梅 刘春招 隋雨桐 皇甫海全 魏东 YU Hai-Rui;WANG Lai-Ping;DENG Qi-Mei;LIU Chun-Zhao;SUI Yu-Tong;HUANGFU Hai-Quan;WEI Dong(Shenzhen Hospital,Shanghai University of Traditional Chinese Medicine,Shenzhen 518009 Guangdong,China;Shenzhen Hospital of Southern Medical University,Shenzhen 518101 Guangdong,China)

机构地区：[1]上海中医药大学深圳医院,广东深圳518009 [2]南方医科大学深圳医院,广东深圳518101

出　　处：《广州中医药大学学报》2024年第6期1588-1597,共10页Journal of Guangzhou University of Traditional Chinese Medicine

基　　金：国家自然科学基金资助项目(编号:8210140330);2023年罗湖区软科学研究计划项目(编号:LX202302068,LX202302082,LX202302087)。

摘　　要：【目的】采用网络药理学和分子对接技术探讨炙甘草汤“异病同治”冠心病心律失常和肺纤维化的作用机制。【方法】在中药系统药理学数据库与分析平台(TCMSP)和本草组鉴(HERB)中检索炙甘草汤所有中药有效成分,运用SwissTargetPrediction数据库预测作用靶点,利用Cytoscape软件构建药物-靶点网络图并进行网络拓扑分析得到核心药物靶点。在GeneCards、OMIM数据库中获取冠心病、心律失常和肺纤维化的疾病靶点,利用Venny软件获得中药与疾病交集靶点。交集靶点导入STRING在线数据库构建蛋白相互作用网络,数据导入Cytoscape软件中进行可视化处理并筛选出核心靶点。使用Metascape数据库对交集靶点进行基因本体论(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。对核心交集靶点与核心药物靶点通过CB-DOCK2在线平台进行分子对接验证及绘制热图可视化处理。【结果】共筛选出炙甘草汤活性成分137个,去除重复值共得到对应药物靶点848个。共获得冠心病疾病靶点9962个、心律失常疾病靶点5735个、肺纤维化疾病靶点7722个。Venny平台处理获得药物-疾病交集靶点362个,经网络拓扑分析得出度值较高的潜在核心靶点有GAPDH、IL-6、ALB、STAT3、TNF、MMP-9等。GO功能富集分析显示,炙甘草汤“异病同治”涉及的主要生物过程(BP)有对激素的反应、循环系统过程、磷代谢过程的正调控、对外源性刺激的反应、对有机物的反应等,主要细胞组分(CC)有脂筏、受体复合物、细胞质核周区、树突、薄膜侧面等,主要分子功能(MF)有蛋白激酶活性、激酶结合、蛋白质均聚活性、核受体活性、血红素结合等。KEGG通路富集分析显示,炙甘草汤“异病同治”涉及的主要信号通路有脂质与动脉粥样硬化、钙信号通路、cAMP信号通路、胰岛素抵抗、cGMP-PKG信号通路、JAK-STAT信号通路、NF-κB�Objective To explore the mechanism of‘homotherapy for heteropathy'Zhigancao Decoction in the treatment of coronary heart disease arrhythmia and pulmonary fibrosis by network pharmacology and molecular docking technology.Methods All the active components of Zhigancao Decoction were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Herbal Compendium(HERB).The SwissTargetPrediction database was used to predict the targets.Cytoscape software was used to construct the drugs-targets network diagram and network topology analysis was performed to obtain the core drug targets.The disease targets of coronary heart disease,arrhythmia and pulmonary fibrosis were obtained in GeneCards and OMIM databases,and the intersection targets of Chinese medicine and disease were obtained by Venny software.The intersection targets were imported into the STRING online database to construct a proteinprotein interaction network,and the data were imported into Cytoscape software for visualization and screening of core targets.Gene ontology(CO)function enrichment analysis and kyto encyclo-pedia of genes and genomes(KEGG)pathway enrichment analysis were performed on the intersection targets using the Metascape database.Molecular docking verification and heat map visualization were performed on the core intersection target and the core drug target through the CB-DOCK2 online platform.Results A total of 137 active components of Zhigancao Decoction were screened out,and 848 corresponding drug targets were obtained by removing repeated values.A total of 9962 targets of coronary heart disease,5735 targets of arrhythmia and 7722 targets of pulmonary fibrosis were obtained.A total of 362 drug-disease intersection targets were obtained by Venny platform processing.The potential core targets with higher degree values were GAPDH,IL-6,ALB,STAT3,TNF,MMP-9 and so on by network topology analysis.GO functional enrichment analysis showed that the main biological processes(BP)involved in Zhigancao D

关 键 词：炙甘草汤 冠心病心律失常 肺纤维化 异病同治 网络药理学 机制研究 

分 类 号：R285.5[医药卫生—中药学]