石斛碱通过作用于SRC调控氧化应激干预糖尿病肾病的机制研究OA北大核心
The mechanism of dendrobine intervenes in diabetic kidney disease by acting on SRC to regulate oxidative stress
目的:探讨石斛碱通过调控氧化应激干预糖尿病肾病(DKD)的作用机制.方法:利用OMIM等数据库检索DKD靶点,使用PharmMapper、SuperPred、ChemMapper和ChEMBL数据库获得石斛碱靶点,通过GeneCards、OMIM数据库检筛选氧化应激相关靶点,并取交集靶点.交集靶点导入STRING数据库获取靶标相互联系以构建PPI,利用MCC拓扑算法分析获取关键靶点.关键作用靶点通过DAVID平台进行基因本体论(GO)分析、京都基因与基因组百科全书(KEGG)富集分析.通过SangerBox平台进行糖尿病肾病临床相关性分析、基因差异表达分析以及ROC分析.将筛选得到的关键靶点通过分子对接和分子动力学模拟进行验证.采用Western Blot实验进行实验验证.结果:获得DKD-石斛碱-氧化应激交集靶点102个,并筛选出 15个关键基因;通过临床相关性分析筛选出 11个有临床意义的关键基因;通过差异表达和ROC分析发现CASP3、CXCR4、ESR1、KDR、SRC差异表达明显,且SRC最具有诊断价值(AUC=0.86,P<0.05);分子对接及分子动力学模拟分析结果发现SRC与石斛碱结合能力最强,且配合物较稳定.Western Blot实验结果表明,与对照组相比SRC和P-SRC在DKD中表达上调(P<0.05),石斛碱可降低其的表达.结论:石斛碱可以通过作用于SRC调控氧化应激干预糖尿病肾病.
Objective:To investigate the mechanism of dendrobine in diabetic kidney disease(DKD)by regulating oxidative stress.Methods:DMIM and other databases were used to retrieve DKD targets,PharmMapper,SuperPred,ChemMapper and ChEMBL databases were used to obtain Dendrobine base targets,and oxidative stress-related targets were screened by GeneCards and OMIM databases,and intersecting targets were obtained.The intersection targets were imported into the STRING database to obtain the interconnection of the targets to construct PPI,and the key targets were analyzed by MCC topology algorithm.Gene ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were performed on key tar-gets through the DAVID platform.The SangerBox platform was used to analyze the clinical correlation of diabetic nephropathy,gene differential expression analysis and ROC analysis.The key targets obtained from the screening were verified by molecular docking and molecular dynamics simulations.Western blot experiments were used for verification.Results:A total of 102 DKD-dendrobine-oxidative stress intersection targets were obtained,and 15 key genes were screened.11 clinically significant key genes were screened through clinical correlation analysis.The differential expression and ROC analysis showed that CASP3,CXCR4,ESR1,KDR and SRC were differentially expressed,and SRC had the most diagnostic value(AUC=0.86,P<0.05).The re-sults of Western blot experiments showed that the expression of SRC and P-SRC was up-regulated in DKD(P<0.05)compared with the control group,and the expression of dendrobine was reduced.Conclusion:Dendrobine can intervene in diabetic kidney disease by acting on SRC to regulate oxidative stress.
李军;薛铃芝;马群;张楠楠
贵州中医药大学基础医学院,贵州 贵阳 550025贵州中医药大学基础医学院,贵州 贵阳 550025贵州中医药大学基础医学院,贵州 贵阳 550025贵州中医药大学基础医学院,贵州 贵阳 550025
中医学
糖尿病肾病石斛碱氧化应激网络药理学分子对接
Diabetic kidney diseaseDendrobineOxidative stressNetwork pharmacologyMolecular docking
《海南医科大学学报》 2025 (1)
41-50,10
This study was supported by the Guizhou Provincial Basic Research Program(Qiankehe Foundation-ZK[2023]General 428)Innovation Project for Graduate Students at Guizhou University of TCM(YCXKYS2023004)贵州省基础研究计划(自然科学)[黔科合基础-ZK(2023)一般 428]2023 年贵州中医药大学研究生教育创新计划项目(YCXKYS2023004)
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