钠-葡萄糖协同转运蛋白-2抑制剂心肾保护作用机制的网络药理学研究  

Network pharmacological study of the mechanism of cardiorenal protection of sodium-glucose cotransporter-2 inhibitors

作　　者：巴文强 李艳 朱文山 李梦媛[3] BA Wenqiang;LI Yan;ZHU Wenshan;LI Mengyuan(Department of Pharmacy,Central People's Hospital of Ji'an,Jiangxi Province,Ji'an343000,China;Department of Psychiatry,Ji An Third People's Hospital,Jiangxi Province,Ji'an343000,China;Department of Pharmacy,the Second Affiliated Hospital of Nanjing Medical University,Jiangsu Province,Nanjing210011,China)

机构地区：[1]江西省吉安市中心人民医院药剂科,江西吉安343000 [2]江西省吉安市第三人民医院心理科,江西吉安343000 [3]南京医科大学第二附属医院药学部,江苏南京210011

出　　处：《中国当代医药》2023年第10期18-21,F0003,F0004,共6页China Modern Medicine

基　　金：江西省吉安市指导性科技计划项目(20222-026804)。

摘　　要：目的基于网络药理学研究钠-葡萄糖协同转运蛋白-2抑制剂(SGLT-2i)心肾保护的作用机制。方法通过相关数据库搜索SGLT-2i与疾病相关的靶点,应用STRING 11.5数据库构建蛋白质-蛋白质相互作用(PPI)网络,使用CytoHubba插件得到关键靶点,利用Metascape数据库进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析,利用CB-Dock平台进行分子对接。结果共预测SGLT-2i靶点450个,获得疾病靶点1221个,交集靶点54个,关键靶点为丝裂原活化蛋白激酶1(MAPK1)、表皮生长因子受体(EGFR)、RAC-α丝氨酸/苏氨酸蛋白激酶(AKT1)等。KEGG结果显示,关键通路可能是糖尿病并发症中的晚期糖基化终产物-糖基化终产物受体信号通路、酪氨酸蛋白激酶-信号转导和转录激活因子信号通路等。分子对接显示,SGLT-2i与关键靶点结合能力较好。结论本研究初步推测了SGLT-2i多靶点、多通路的心肾保护作用机制,这为该类药物心肾保护机制提供了新的认识。Objective Study on the mechanism of cardiorenal protection of sodium-glucose cotransporter-2 inhibitor(SGLT-2i)based on network pharmacology.Methods SGLT-2i disease-related targets were searched through relevant databases,STRING 11.5 database was used to build protein-protein interaction(PPI)network,CytoHubba plug-in was used to obtain key targets,Metascape database was used to conduct Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis,and CB-Dock platform was used to conduct molecular docking.Results A total of 450 SGLT-2i targets were predicted,1221 disease targets and 54 intersection targets were obtained,and the key targets were mitogen-activated protein kinase 1(MAPK1),epidermal growth factor receptor(EGFR)and RAC-alpha serine/threonine-protein kinase(AKT1),etc.KEGG results showed that the key pathways might be the late glycation end products receptor signaling pathway,tyrosine protein kinase signal transduction and transcription activator signaling pathway in the complications of diabetes.Molecular docking shows that SGLT-2i has good binding ability with key targets.Conclusion This study preliminarily speculated the cardiorenal protective mechanism of SGLT-2i with multiple targets and pathways,which provided a new understanding for the cardiorenal protective mechanism of such drugs.

关 键 词：钠-葡萄糖协同转运蛋白-2抑制剂 心肾保护 网络药理学 分子对接 作用机制 

分 类 号：R285[医药卫生—中药学]