基于网络药理学探析黄连治疗糖尿病肾病的作用机制

Mechanism of Coptidis Rhizoma in the Treatment of Diabetic Nephropathy Based on Network Pharmacology

目的基于网络药理学探讨黄连治疗糖尿病肾病(DN)的作用机制。方法在中药系统药理学数据库与分析平台(TCMSP)中筛选黄连的活性成分及靶点基因,在GendCards、OMIM数据库中寻找DN相关靶点基因,取黄连靶点基因与DN相关靶点基因的交集,筛选出黄连和DN共同作用的靶点基因。通过Cytoscape 3.5.0软件,构建疾病-活性成分-靶点基因的相互网络。通过String平台构建蛋白互作(PPI)网络,绘制PPI网络柱状图,对靶点基因进行基因本体论(GO)富集通路及京都基因和基因组百科全书(KEGG)通路进行分析。结果从黄连中筛选获得14个活性成分,与DN相关的关键靶点基因101个,KEGG富集通路主要包括AGE-RAGE信号通路、流体剪切应力和动脉粥样硬化信号通路、缺氧诱导因子-1(HIF-1)信号通路等,推测黄连可能是通过以上通路等对DN产生干预作用。结论黄连具有多个活性成分,能通过多个靶点、多个通路发挥治疗DN的作用。

Objective To investigate the mechanism of Coptidis Rhizoma in the treatment of diabetic nephropathy(DN)based on network pharmacology.Methods The active components and target genes of Coptidis Rhizoma were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and the DN-related target genes were searched in GendCards and Online Mendelian Inheritance in Man(OMIM)databases.The target genes of Coptidis Rhizoma were intersected with the DN-related target genes,and the target genes of Coptidis Rhizoma and DN were screened.Cytoscape 3.5.0 software was used to construct an inter-network of disease-active component-target genes.The protein-protein interaction(PPI)network was constructed by the String platform,and the PPI network histogram was drawn.The gene ontology(GO)enrichment pathway and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway of target genes were analyzed.Results A total of 14 active components were screened from Coptidis Rhizoma,and 101 key target genes related to DN.KEGG enrichment pathways mainly included advanced glycation end products(AGE)-receptor for AGE(RAGE)signal pathway,fluid shear stress and atherosclerosis signal pathway,hypoxia inducible factor-1(HIF-1)signal pathway,etc.It is speculated that Coptidis Rhizoma might interfere with DN through the above pathways.Conclusion Coptidis Rhizoma has multiple active components,which can play a role in the treatment of DN through multiple targets and pathways.