[关键词]
[摘要]
目的 运用计算机网络药理学方法虚拟筛选尿毒灵复方治疗糖尿病肾病的可能的活性成分及作用靶点,探讨尿毒灵对治疗糖尿病肾病的潜在作用机制。方法 通过人类基因数据库(GeneCards),治疗靶点数据库(TTD),比较毒性遗传学数据库(CTD),基因疾病关联数据库(DisGeNET),DrugBank数据库等收集与疾病相关的作用靶点;并通过中药系统药理学分析平台(TCMSP)获得尿毒灵中可能的活性成分及其对应的靶点。利用Bioinformatics & Evolutionary Genomics平台筛选出药物与疾病共有靶点,借助Cytoscape3.7.1软件构建“成分-作用靶点”网络。运用蛋白质相互作用网络数据库(String)构建蛋白质间相互作用网络(PPI)。最后通过功能注释生物信息学分析平台(DAVID 6.8)进行尿毒灵与糖尿病肾病相关靶基因的基因本体(gene ontology,GO)功能分析和京都基因与基因组百科全书(KEGG)通路富集分析,并将结果进行可视化展示。结果 通过筛选得到67个药物活性成分,共涉及152个作用靶点,与疾病靶点相关的化学成分有39个,得到尿毒灵-糖尿病肾病共同靶点46个,这些共同靶点主要富集于130个生物过程和78条信号通路上,表明尿毒灵的多个成分通过多条信号通路发挥防治糖尿病肾病的作用。结论 利用网络药理学方法分析中药复方的作用机制,可以体现中药多成分-多靶点-多途径的特点,为中药复方的作用机制和物质基础提供参考和依据。
[Key word]
[Abstract]
Objective To use a computer network pharmacology method to virtually screen the possible active ingredients and targets of action of Niaoduling formula compound for the treatment of diabetic nephropathy and to explore the potential mechanism of action of Niaoduling formula for the treatment of diabetic nephropathy.Methods We collected disease-related targets through human gene database (GeneCards), therapeutic target database (TTD), comparative toxicity genetics database (CTD), genetic disease association database (DisGeNET), DrugBank database, etc. We also obtained the possible active ingredients and their corresponding targets in Niaoduling formula through the Traditional Chinese Medicine System Pharmacology Platform (TCMSP). The potential active ingredients and their corresponding targets were obtained through TCMSP. We used the Bioinformatics & Evolutionary Genomics platform to screen the drug-disease targets and constructed the “component-target” network with the help of Cytoscape 3.7.1 software. The protein-protein interaction (PPI) network was constructed using the protein interaction network database (String). Finally, the gene ontology (GO) functional analysis and Kyoto Encyclopedia of Genomics (KEGG) pathway enrichment analysis of target genes related to uropoietin and diabetic nephropathy were performed by functional annotation bioinformatics analysis platform (DAVID 6.8), and the results were visualized.Results The results showed that there were 67 active ingredients, involving 152 targets, and 39 chemical components related to the disease targets, and 46 common targets were obtained for Niaoduling-diabetic nephropathy, which were mainly enriched in 130 biological processes and 78 signaling pathways, indicating that several components of Uralin exerted their effects on diabetic nephropathy through multiple signaling pathways.Conclusion The analysis of the mechanism of action of Chinese medicine compound using network pharmacology method can reflect the characteristics of multi-component-multi-target-multi-pathway of Chinese medicine, which can provide reference and basis for the mechanism of action and material basis of Chinese medicine compound.
[中图分类号]
R256
[基金项目]