目的：通过分析C57BL/KsJ-db/db小鼠的基因表达数据库确定与糖尿病视网膜病变(DR)相关的生物标志物、蛋白质编码基因、转录因子和生物通路。方法：从基因表达综合数据库中选择并获得db/db小鼠GSE55389芯片数据集，鉴定视网膜中差异表达基因(DEGs)，采用基因本体(GO)分析、KEGG通路富集分析、基因集富集分析(GSEA)、蛋白质相互作用(PPI)网络的构建和转录因子(TFs)预测等综合生物信息学分析方法阐明所鉴定基因的生物学功能。结果：db/db小鼠模型病变视网膜中发现38个上调、28个下调DEGs。GO分析表明，下调基因在眼发育功能中较丰富，差异基因没有发现明显的KEGG通路。蛋白质相互作用网络显示DR中有7个hub基因，GSEA分析在P<0.1下发现12条上调和6条下调通路。预测了5种上调和8种下调的转录因子及其结合位点。结论：鉴定DR相关基因及通路有助于了解DR的发展机制，预测部分转录因子如Runx2、Ppara、MafA、Gata2、Hoxa13可能是治疗DR的有效靶标。

AIM: To identify the related biomarkers, coding genes, transcription factors and biological pathways in diabetic retinopathy(DR)via analysis of the gene expression database of C57BL/KsJ-db/db mice.METHODS: We selected and obtained microarray datasets from the Gene Expression Omnibus database to identify different expressed genes in retinas with db/db mouse model. Integrated bioinformatic analysis was used to clarify biological functions of the identified genes, including Gene Ontology(GO), the construction of a protein-protein interaction network, transcription factor, and gene set enrichment analysis.RESULTS:Totally 38 genes were found upregulated accompanied by down-regulation of 28 genes in the retina of db/db mouse. GO analysis showed that the down-regulated genes were enriched in eye development whereas there was no significant KEGG pathway identified by the differentially expressed genes. The protein-protein interaction network revealed seven hub genes involved in DR. Moreover, GSEA showed 12 up-regulated pathways with 6 down-regulated pathways(P<0.1), predicting up-regulation of 5 transcription factors(TFs)and down-regulation of 8 TFs along with their binding sites. CONCLUSION: The pathways and genes discovered herewith are beneficial to clarify the mechanism of DR and the part of transcription factors identified during the study, such as Runx2, Ppara, MafA, Gata2 and Hoxa13, may provide promising targets for future noval treatment of DR.

国家自然科学基金资助项目(No.81371061)