基于网络药理学探讨三叶糖脂清治疗2型糖尿病的作用机制

Mechanism of Sanye Tangzhiqing Tablet in treating type 2 diabetes mellitus based on network pharmacology

关键词:  三叶糖脂清  2型糖尿病  网络药理学  KEGG通路富集  潜在靶点

Key words:  Sanye Tangzhiqing Tablet  T2DM  network pharmacology  KEGG pathway enrichment  potential target

摘要:

[目的] 探讨三叶糖脂清片治疗2型糖尿病（T2DM）的作用机制。[方法] 使用网络检索平台中药系统药理学数据库与分析平台（TCMSP）的SYSDT运算确定三叶糖脂清的有效活性成分与相关靶点信息，使用Perl语言并结合Uniprot数据库，最终得到三叶糖脂清的基因靶点缩写。利用人类表型本体论（HPO）数据库和Genecard数据库检索T2DM相关靶基因。使用STRING数据库分析并结合Cytoscape 3.7.1软件绘制靶点蛋白互作网络（PPI），借助Perl语言转换为基因编号，利用R语言的Bioconducor程序包进行京都基因与基因组百科全书（KEGG）通路富集分析和基因功能分析（GO）富集分析。探讨三叶糖脂清的多重药理作用机制，为下一步实验验证奠定基础。[结果] 通过网络参数分析确定了三叶糖脂清含有80个活性成分，对应82个生物靶点。通过Genecard和HPO数据库得到540个T2DM靶点，其中Genecard数据库中选取Score值大于30的靶点。两者对比提取重叠靶点，并与80个活性成分构建出“活性成分-靶点”网络。揭示了三叶糖脂清活性成分与T2DM靶点之间的相互作用，并对重叠靶点的蛋白互作网络（PPI）进行分析，明确药物影响疾病的关键靶点。此外，对重叠靶点进行KEGG通路富集分析和GO功能富集分析，探索了三叶糖脂清治疗T2DM的作用机制。[结论] 三叶糖脂清治疗T2DM具有多成分、多靶点、多途径的特点，为进一步开展三叶糖脂清抗T2DM作用的分子机制研究提供了新思路和科学依据。

Abstract:

[Objective] To investigate the mechanism of Sanye Tangzhiqing Tablets in the treatment of type 2 diabetes mellitus (T2DM).[Methods] The SYSDT operation of TCMSP (Pharmacology database and analysis platform of traditional Chinese medicine system) was used to determine the effective active ingredients and related targets information of Sanye Tangzhiqing Tablets. Perl language and UniProt database were used to get the gene target reduction of Sanye Tangzhiqing Tablets. The HPO (human phenotype ontology) database and GENECARD database were used to retrieve the target genes related to type 2 diabetes. The PPI (protein interaction network) was drawn by using string database analysis and Cytoscape 3.7.1 software. The PPI was converted into gene number by perl language. The pathway enrichment analysis and go enrichment analysis of KEGG (Kyoto Encyclopedia of gene and genome) were carried out by using bioconducor package of R language. It laid the foundation to explore the multiple pharmacological mechanism of Sanye Tangzhiqing Tablets by the next experimental verification.[Results] Through the network parameter analysis,80 active components were identified,corresponding to 82 biological targets. The 540 T2DM targets were obtained from GENECARD and HPO databases,among which targets with score greater than 30 were selected from GENECARD database. The overlapping targets were extracted and compared with 80 active components to construct "active component target" network. The interaction between the active components of triglyceride and T2DM targets was revealed,and the PPI of overlapping targets was analyzed to identify the key targets of drug affecting diseases. In addition,the enrichment analysis of KEGG pathway and go function was carried out to guide the future experiments.[Conclusion] Sanye Tangzhiqing Tablets has the characteristics of multi-component,multi-target and multi-channel in the treatment of T2DM,which provides a new idea and scientific basis for further research on the molecular mechanism of the anti-diabetic effect of Sanye Tangzhiqing Tablets.