摘要
目的:探讨糖尿病患者肝脏与正常对照肝脏基因表达谱的变化,并进行代谢通路生物信息学分析。方法:应用Affymetrix的Human Genome U133A array芯片检测糖尿病肝脏组织(n=2)和正常对照肝脏组织(n=2)的基因表达谱变化,通过DAVID分析平台对芯片监测到的表达上调的基因进行KEGG通路分析,并用RT-PCR验证部分基因的表达情况。结果:以比值大于2或小于-2为准,共有492条基因明显上调,820条基因明显下调;在差异表达明显的前20位基因中,涉及氧化应激、免疫炎症反应和脂代谢。KEGG代谢通路分析显示:该差异表达基因谱符合2型糖尿病的发病机制,其差异表达明显基因的代谢通路涉及胰岛素信号通路、脂代谢、补体和凝血系统、糖代谢、粘附功能和细胞因子和受体的相互作用,RT-PCR证实差异表达明显基因SOD2mRNA和CRPmRNA确实表达明显上调。结论:糖尿病肝脏与正常肝脏组织基因表达谱的变化在代谢通路上主要表现为在糖、脂代谢和胰岛素信号通路、补体和凝血系统等的改变,肝脏在糖尿病发病机制中的作用可能与其参与糖脂代谢和胰岛素的作用异常有关。
Objective：To investigate gene profile in diabetic liver tissue and perform metabolic pathway analysis among significantly increased or decreased expression gene.Methods： OLigonucleotide array was utilized to screen the defference of gene expression in both diabetic liver and normal liver tissue.KEGG metabolic pathway was performed among significantly increased or decreased gene.RT-PCR was performed to assessthe mRNA level of the gene.Results： Compare with the matched normal tissue,492 genes was upregulated and 820 genes was downregulated in the diabetic liver. Among the first 20 difference gene, they are involved in oxidative stress ,immune and inflammation response and lipid metabolism.KEGG metabolic pathway analysis showed that gene profile of diabetic liver was in accordance with pathway change in type 2 diabetes. Signficantly difference gene was involved in the metabolic pathway such as insulin signaling pathway, complement and coagulation cascades,fructose and mannose, adherens junction, pentose phosphate pathway, lipid metabolism, cytokine and cytokine-receptor interaction. SOD2 mRNA and CRPmRNA was signficanly more upregulated in diabetic liver than in nomal control proved by RT-PCR. Conclution： The change of gene profile was involved in the metabolic pathway such as insulin signaling pathway, complement and coagulation cascades, fructose and mannose, adherens junction, pentose phosphate pathway, lipid metabolism, the role of liver in the pathogenesis may involved in the change of insulin signal pathway, carbohydrate metabolism and lipid metabolism.
出处
《现代生物医学进展》
CAS
2009年第19期3601-3604,共4页
Progress in Modern Biomedicine
基金
国家自然科学基金重点项目(30230380)
上海市科委重大课题(04dz19504)
自然科学基金资助项目(300700385)
关键词
糖尿病
基因芯片
KEGG
代谢通路分析
diabetes mellitus
gene chip
KEGG
metabolism pathway analysis
