黄芪甲苷调控氨基酸代谢抗糖尿病肾损害分子网络机制研究  

Molecular Network Mechanism of Astragaloside Ⅳ Regulating Amino Acid Metabolism in Diabetic Nephropathy

作　　者：戈娜[1] 林韦翰 黄静婷 古秀芬 吴瑕 李顺民[1] GE Na;LIN Weihan;HUANG Jingting;GU Xiufen;WU Xia;LI Shunmin

机构地区：[1]深圳市中医院肾病科,广东深圳518033

出　　处：《新中医》2022年第5期22-28,共7页New Chinese Medicine

基　　金：国家自然科学基金青年项目(81704012)。

摘　　要：目的:应用网络药理技术从氨基酸代谢调控角度分析黄芪甲苷抗糖尿病肾损害网络分子机制。方法:基于前期代谢组学筛选出的与糖尿病肾病进展相关的氨基酸。使用KEGG、PubChem、TCMSP数据库,检索并提取氨基酸及黄芪甲苷的有效靶标基因,采用KEGG pathway数据库进行通路分析;应用Cytoscape绘制黄芪甲苷、氨基酸基因靶标蛋白互作网络图,并提取核心基因靶标。Cytoscape3.7.1软件内在的ClueGO应用进行疾病进展相关氨基酸基因靶标的通路、生物过程、细胞定位、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10个与糖尿病肾病进展密切相关的氨基酸,提取基因靶标82个,参与KEGG通路62条。提取黄芪甲苷基因靶标24个。通过构建PPI网络,拟合黄芪甲苷和氨基酸基因靶标网络,提取核心靶标39个。富集分析结果表明黄芪甲苷和氨基酸核心基因靶标参与调控细胞应激、转录生长因子调控、蛋白质去乙酰化、RNA聚合酶调控、DNA结合调节、细胞周期调控、碳水化合物分解、糖酵解、细胞增殖染色质重塑等生物过程;涉及的细胞定位包括细胞周期蛋白、RNA聚合酶体复合物、常染色质、转录抑制因子、ATP酶复合物、PcG蛋白复合物、组蛋白甲基转移酶、组蛋白去乙酰化酶、SWI/SNF超家族复合物、Sin3复合物、CHD复合物;参与的分子功能有调控组蛋白去乙酰化、DNA转录因子结合、RNA聚合酶结合、转录因子活化、染色质DNA结合、泛素蛋白连接、p53连接、糖皮质受体结合等;核心基因靶标涉及的KEGG通路以调控细胞周期、癌症、自噬通路相关通路为主。结论:黄芪甲苷可能通过调节糖代谢、蛋白、DNA的转录后修饰,在细胞增殖、细胞周期、氧化应激、细胞自噬等多个分子功能层面实施保护糖尿病肾病肾脏的功能。Objective:To analyze the molecular mechanism of astragalosideⅣagainst diabetic renal damage by using network pharmacology technology from the perspective of amino acid metabolism regulation.Methods:Based on previous metabonomics,amino acids related to the progression of diabetic nephropathy were screened.KEGG,PubChem and TCMSP databases were used to search and extract the effective target genes of amino acids and astragalosideⅣ,and KEGG pathway database was used for pathway analysis.The interaction network of astragalosideⅣand amino acid gene target protein was drawn by Cytoscape,and the core gene target was extracted.The ClueGO inherent in Cytoscape3.7.1 software is used to enrich and analyze the pathway,biological process,cell localization and molecular function of amino acid gene targets related to disease progression,and draw the network diagram.Results:A total of 10 amino acids,which were closely related to the progression of diabetic nephropathy,were analyzed.82 of the target genes were extracted,and62 were involved in the KEGG pathway.24 astragaloside gene targets were extracted.By constructing PPI network,fitting astragalosideⅣand amino acid gene target network,39 core targets were extracted.Enrichment analysis showed that astragalosideⅣand amino acid core gene targets were involved in the regulation of biological processes such as cell stress,transcriptional growth factor regulation,protein deacetylation,RNA polymerase regulation,DNA binding regulation,cell cycle regulation,carbohydrate decomposition,glycolysis,cell proliferation and chromatin remodeling.The cell localization involved includes cyclin,RNA polymerase complex,euchromatin,transcription inhibitor,ATPase complex,PcG protein complex,histone methyltransferase,histone deacetylase,SWI/SNF superfamily complex,Sin3 complex and CHD complex.The molecular functions involved include regulating histone deacetylation,DNA transcription factor binding,RNA polymerase binding,transcription factor activation,chromatin DNA binding,ubiquitin protein bi

关 键 词：糖尿病肾病 黄芪甲苷 氨基酸代谢 分子网络机制 肾损害 

分 类 号：R285[医药卫生—中药学]