基于网络药理探究糖尿病肾病进展相关代谢物靶标的分子机制

Exploring the Molecular Mechanism of Metabolite Targets Related to the Progression of Diabetic Nephropathy Based on Network Pharmacology

目的:应用网络药理技术,分析糖尿病肾病进展相关代谢物及其分子靶标和作用机制。方法:基于前期代谢组学筛选出的与糖尿病肾病进展高度相关的代谢物,使用京都基因与基因组百科全书(KEGG)、PubChem数据库,检索提取与代谢物有关的有效靶标基因,并进行通路分析;采用Cytoscape 3.2.1软件ClueGO进行代谢物基因靶标的通路、生物过程、细胞组分、分子功能进行富集分析,并绘制网络图。结果:本研究共分析了31个与糖尿病肾病进展相关的代谢物;应用KEGG和PubChem数据库,共提取了31个代谢物,涉及代谢通路82条,涉及基因靶标252个;代谢物的基因靶标共涉及157条通路。代谢物基因靶标主要集中在谷氨酸、色氨酸、苯丙氨酸等代谢物。基于代谢物-基因靶标网络图核心节点进行解析,提示谷氨酸是连线最多的节点,其次是酪氨酸、谷氨酰胺、色氨酸等;连线最多的通路包括糖酵解/糖异生,脂肪酸降解、氨基酸合成等;最集中的基因靶标为NOS2、NOS3、ALDH7A1等。基因靶标的富集分析结果表明,代谢物基因靶标主要集中在氨基酸代谢、脂肪酸、氮代谢等。基因靶标涉及的细胞组分分析提示糖尿病肾病进展主要与线粒体、突触膜、突触前膜等细胞部位异常有关。疾病进展涉及的分子功能包括氨基酸、羧酸、维生素拼接等。结论:通过对代谢物基因靶标进行深入的网络分析提示,氨基酸代谢异常在糖尿病肾病进展中至关重要,是参与机体免疫代谢调节的关键节点。

Objective:To analyze metabolites related to the progression of diabetic nephropathy and their molecular targets and mechanisms of action based on network pharmacology technology.Methods:Metabolites that were highly correlated with the progression of diabetic nephropathy were screened out based on early metabolomics.KEGG and PubChem databases were used to retrieve and extract the effective target genes of metabolization and conduct pathway analysis;Cytoscape 3.2.1 software ClueGO were used to conduct enrichment analysis of pathways,biological processes,cell components,and molecular functions of metabolite gene targets,and we drew network diagrams.Results:A total of 31 metabolites related to the progression of diabetic nephropathy were analyzed in the study.By using the KEGG and PubChem databases,a total of 31 metabolites were extracted,involving 82 metabolic pathways and 252 gene targets;the gene targets of metabolites involved a total of 157 pathways.Metabolite gene targets were mainly concentrated in metabolites such as glutamate,tryptophan,and phenylalanine.Analysis based on the core nodes of the metabolite-gene target network diagram,suggests that glutamate was the most connected node,followed by tyrosine,glutamine,tryptophan,etc.;the most connected pathways included glycolysis/sugar Xenobiotics,fatty acid degradation,amino acid synthesis,etc.;the most concentrated gene targets were NOS2,NOS3,ALDH7A1,etc.The enrichment analysis results of gene targets showed that metabolite gene targets were mainly concentrated in amino acid metabolism,fatty acid,nitrogen metabolism etc.Analysis of the cellular components involved in gene targets suggestd that the progression of diabetic nephropathy was mainly related to the abnormalities of mitochondria,synaptic membranes,presynaptic membranes and other cellular parts.The molecular functions involved in disease progression included amino acids,carboxylic acids,and vitamin splicing.Conclusion:Through in-depth network analysis of metabolite gene targets,it is suggested that abnormal amino acid metabolism is very important in the progression of diabetic nephropathy and is a key node involved in the regulation of immune metabolism of the body.