2型糖尿病模型大鼠肝脏脂代谢相关基因的筛选及生物信息学分析

肝的脂肪代谢异常和胰岛素抵抗（insulin resistance，IR）对促进2型糖尿病（type 2 diabetes mellitus，T2DM）的发生与发展具有显著影响。但此过程复杂，参与调控基因目前尚未完全清楚。有研究表明，脂肪酸分解、氨基酸代谢、肝糖原合成等生物过程对糖尿病的形成具有促进作用。为了阐明这一调控机制，本文通过基因芯片技术研究GK（Goto-Kakizaki）大鼠和WKY（Wistar-Kyoto）大鼠肝差异基因对肝的脂肪代谢和胰岛素抵抗的影响，探讨可引起2型糖尿病发病的分子机制。从基因表达数据库（GEO）获取GSE13271基因表达谱，并对原始数据进行标准化处理。通过GO（Gene Ontology）、KEGG（Kyoto Encyclopedia of Genes and Genomes enrichment）、String和Cytoscape软件对差异表达基因进行功能分析。结果从GK和WKY大鼠中分别获得179和278个差异基因，同时从排名前10的路径中筛选出21个差异基因(Aldh1a1, Cyp2c22, bp2,Fabp7,Cyp4a3, Acot1, Acot2,Hsd17b2, Ech1, Hmgcl,Bdh1, Crot, Pex11a, Cpt1a, Hadhb, Gda, Elovl2, Prodh, Agpat3, Sardh, Pigu)，将这些基因与前10个的GO term取交集。最终得到10个显著差异基因(Aldh1a1, Fabp2, Acot1, Acot2, Ech1, Hmgcl, Bdh1, Crot, Cpt1a, Hadhb),功能分析结果显示，肝组织相关基因通过一系列生物过程对肝的脂肪代谢和胰岛素抵抗产生调节作用，从而也为临床糖尿病的治疗以及新作用靶点的发现提供更多参考依据。

Screening and Bioinformatic Analysis of Genes Related to Lipid Metabolism in Liver of Rats with Type 2 Diabetes Mellitus

The abnormal metabolism of liver fat and insulin resistance (IR) plays important roles in the occurrence and development in type 2 diabetes mellitus (T2DM). However, the process is complicated and the genes involved in regulation are not clear. Some studies have shown that the biological processes such as fatty acids decomposition, amino acid metabolism and liver glycogen synthesis can promote the formation of diabetes mellitus. In order to understand the detailed molecular mechanisms of T2DM pathogenesis, the differentially expressed hepatic genes on liver lipid metabolism and IR were studied by cDNA microarray between GK (Goto-Kakizaki) and WKY (Wistar-Kyoto) rats. The expression profile of GSE13271 was downloaded and standardized from gene expression omnibus (GEO). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes enrichment (KEGG), string as well as Cytoscape software was applied to interpret the function of differentially regulated genes. Finally 179 and 278 differentially expressed genes were obtained from GK rats and WKY rats, respectively. A total of 21 differentially expressed genes (Aldh1a1, Cyp2c22, Fabp2, Fabp7, Cyp4a3, Acot1, Acot2, Hsd17b2, Ech1, Hmgcl, Bdh1, Crot, Pex11a, Cpt1a, Hadhb, Gda, Elovl2, Prodh, Agpat3, Sardh, Pigu) were screened from the top ten pathways. The intersection with top ten GO term and 10 most significantly differentially expressed genes (Aldh1a1, Fabp2, Acot1, Acot2, Ech1, Hmgcl, Bdh1, Crot, Cpt1a, Hadhb) were acquired. The functional analysis showed that these genes were related to liver regulation of lipid metabolism and IR through a series of biological processes, which may provide further information for finding potential targets for T2DM.