基于网络药理学和SPR检测探讨生脉散治疗2型糖尿病合并冠心病的作用机制  

Mechanism of Shengmaisan in Treating Type 2 Diabetes Mellitus with Coronary Heart Disease Based on Network Pharmacology and SPR Assay

作　　者：陈沫良 王晓珍 许光辉 李知瑾 CHEN Moliang;WANG Xiaozhen;XU Guanghui;LI Zhijin(Xiamen Health and Medical Big Data Center/Xiamen Medicine Research Institute/Xiamen Key Laboratory of Natural Medicine Research and Development,Xiamen 361008,Fujian,China;College of Pharmacy,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,Fujian,China)

机构地区：[1]厦门市健康医疗大数据中心/厦门市医药研究所/厦门市天然药物研究与开发重点实验室,福建厦门361008 [2]福建中医药大学药学院,福建福州350122

出　　处：《医学信息》2024年第20期1-10,共10页Journal of Medical Information

基　　金：厦门市医疗卫生指导性项目(编号:3502Z20214ZD1304)。

摘　　要：目的探讨生脉散治疗2型糖尿病(T2DM)合并冠心病(CHD)的作用机制。方法应用TCMSP、BATMAN-TCM和Uniprot数据库检索生脉散药效成分及对应靶点,应用Genecards、Drugbank和TTD数据库检索T2DM和CHD靶点基因,运用Venny2.1.0工具得到疾病交集靶点,采用Cytoscape3.9.1软件,建立药效物质-成分-靶点的网络图谱,通过STRING构建PPI网络,并获取排名前10的关键靶点基因,通过R语言ClusterProfiler包进行GO功能和KEGG通路分析,使用Discovery Studio软件完成分子对接,最后完成SPR检测实验验证。结果获得生脉散207个药效成分,对应1643个相关作用靶点;T2DM疾病靶点2663个,CHD疾病靶点1206个,疾病-药物交集靶点337个;最终获得3个关键靶点:AKT1、CTNNB1、ESR1;GO和KEGG分析发现涉及的生物学通路主要有MAPK、AGE-RAGE、TNF等信号通路;将上述得到的结果进行分子对接,并选取AKT1蛋白和相关有效成分完成表面等离子共振SPR结合检测,结果显示均有较好活性。结论生脉散可能从多成分、多靶点和多途径调控糖脂代谢、改善氧化应激等方面来发挥治疗T2DM合并CHD的作用。Objective To explore the mechanism of Shengmaisan on the treatment of type 2 diabetes mellitus(T2DM)with coronary heart disease(CHD).Methods The TCMSP,BATMAN-TCM and Uniprot databases were used to retrieve the active components and corresponding targets of Shengmaisan.The Genecards,Drugbank and TTD databases were used to retrieve the target genes of T2 DM and CHD.The Venny2.1.0 tool was used to obtain the disease intersection targets.Cytoscape 3.9.1 software was used to establish a network map of active substances-components-targets.The PPI network was constructed by STRING,and the top 10 key target genes were obtained.GO function and KEGG pathway analysis were performed through the R voice ClusterProfiler package,and molecular docking was completed using Discovery Studio software.Finally,the SPR assay experiment was completed.Results There were 207 effective components in Shengmai Powder,corresponding to 1643 related targets.There were 2663 T2DM disease targets,1206 CHD disease targets,and 337 disease-drug intersection targets.Finally,three key targets were obtained:AKT1,CTNNB1,ESR1;GO and KEGG analysis found that the biological pathways involved mainly include MAPK,AGE-RAGE,TNF and other signaling pathways;the above results were subjected to molecular docking,and AKT1 protein and related active ingredients were selected to complete the surface plasmon resonance SPR binding detection,and the binding results showed that all of them had good activity.Conclusion Shengmaisan may play a role in the treatment of T2DM complicated with CHD from the aspects of multi-component,multi-target and multi-channel regulation of glucose and lipid metabolism,improvement of oxidative stress,etc.

关 键 词：2型糖尿病 冠心病 生脉散 网络药理学 SPR检测 

分 类 号：R259[医药卫生—中西医结合]