摘要
目的:探析二至丸治疗糖尿病肾病(Diabetic Nephropathy,DN)的可能机制。方法:利用中药系统药理学数据库与分析平台(TCMSP)搜集二至丸的主要活性成分及作用靶点,通过GeneCards数据库、OMIM数据库、PharmGKB数据库、TTD数据库、DrugBank数据库筛选DN有关基因,用在线平台Venny 2.1.0构建韦恩图,得到二至丸治疗DN的靶点,将选取的交集靶点导入STRING数据库构建蛋白质–蛋白质相互作用网络图,并将结果数据导入Cytoscape 3.9.0进行可视化。采用DAVID数据库对交集基因进行基因本体论(GO)功能和京都基因与基因组百科全书(KEGG)通路富集分析,最后利用分子对接技术进行验证。结果:筛选二至丸中21个有效成分,预测治疗DN的相关靶点278个,GO分析和KEGG通路富集分析结果显示,二至丸治疗DN作用机制主要涉及细胞凋亡过程的负调控、RNA聚合酶Ⅱ启动子转录的正调控等生物过程,并通过脂质和动脉粥样硬化、表皮生长因子受体(Epidermal Growth Factor Receptor,EGFR)酪氨酸激酶抑制剂耐药性、糖尿病并发症中的晚期糖基化终末产物–糖基化终末产物受体(Advanced Glycation End–product–Receptor for Advanced Glycation End Products,AGE–RAGE)信号通路、趋化因子信号通路、磷脂酰肌醇3激酶(Phosphatidylinositol 3–kinase,PI3K)–蛋白激酶B(Akt)信号通路、细胞凋亡等信号通路进行调控。分子对接结果显示,灯盏花苷D、木犀草素等潜在活性成分和肿瘤蛋白p53(Tumor Protein p53,TP53)、信号转导因子和转录激活因子3(Signal Transducer and Activator of Transcription 3,STAT3)等关键靶蛋白有较强的亲和能力。结论:二至丸的有效成分可能通过作用于TP53、STAT3等靶点直接或间接影响脂质和动脉粥样硬化、EGFR酪氨酸激酶抑制剂耐药性等信号通路,从而发挥治疗DN的作用。
Objective:To explore the possible mechanism of Erzhi Wan(二至丸)in treating diabetic nephropathy.Methods:TCMSP was used to collect the main active ingredients and targets of Erzhi Wan.GeneCards database,OMIM database,PharmGKB database,TTD database and DrugBank database were selected to screen the genes related to diabetic nephropathy.Venn map was constructed using Venny 2.1.0 online platform.The targets of Erzhi Wan for treating diabetic nephropathy was obtained,and the selected intersection target was imported into STRING database to construct a protein-protein interaction network diagram,and the resulting data was imported into Cytoscape 3.9.0 for visualization.The GO function and KEGG pathway enrichment of the intersection genes were analyzed using DAVID database,and finally verified by molecular docking technology.Results:Twenty-one active components of Erzhi Wan were screened,and 278 related targets for the treatment of diabetic nephropathy were predicted.GO analysis and KEGG pathway enrichment results showed that the mechanism of action of Erzhi Wan for the treatment of diabetic nephropathy mainly involved the negative regulation of apoptosis process and the positive regulation of RNA polymerase II promoter transcription.It is also regulated by lipid and atherosclerosis,EGFR tyrosine kinase inhibitor resistance,AGE-RAGE signaling pathway in diabetic complications,chemokine signaling pathway,PI3K-Akt signaling pathway,apoptosis and other signaling pathways.Molecular docking results showed that lucidumoside D,luteolin and other potential active components had strong affinity for TP53,STAT3 and other key target proteins.Conclusion:The active components of Erzhi Wan may directly or indirectly affect the signaling pathways of lipid and atherosclerosis and EGFR tyrosine kinase inhibitor resistance by acting on TP53,STAT3 and other targets,playing a role in the treatment of diabetic nephropathy.
出处
《中医临床研究》
2025年第11期85-91,共7页
Clinical Journal Of Chinese Medicine
基金
2023年省基础研究计划项目(省级)(黔科合基础-ZK[2023]一般414)
2023年贵州中医药大学学术新苗项目(校级)(贵科合学术新苗[2023]-23号)
2019年博士启动资金(校级)(贵中医博士启动[2019]29号)。
关键词
二至丸
糖尿病肾病
网络药理学
分子对接
靶点预测
Erzhi Wan
Diabetic nephropathy
Network pharmacology
Molecular docking
Target prediction
