2型糖尿病早期大鼠外周神经节基因表达谱分析

Analysis of gene expression profile of peripheral ganglia in early stage type Ⅱ diabetic rats

糖尿病神经病变(Diabetic neuropathy,DN)是糖尿病在神经系统发生的多种并发病变的总称。文章旨在筛选2型糖尿病早期大鼠外周神经节差异表达的基因。采用Illumina大鼠基因表达芯片,比较糖尿病模型与非糖尿病大鼠外周神经节基因表达谱差异。结果表明,全基因组12 604个已知基因中,158个基因差异表达。糖尿病组与非糖尿病组相比,87个基因表达上调,71个表达下调。对差异表达的基因进行GO分析,发现上调基因所参与的最显著(P<0.001)的几个生物学过程都与神经细胞骨架及运动功能有关;下调基因所参与的最显著的生物学过程主要与"对病毒/生物刺激/其它生物的反应"有关。KEGG(Kyoto encyclopedia of genes and genomes)分析显示,差异表达的基因所参与的最显著(P<0.001)的生物学通路为代谢通路。结果表明:高血糖可导致糖尿病大鼠外周神经节代谢紊乱;高血糖可能通过免疫炎症反应、改变神经细胞骨架及运动功能相关的基因的表达,继而损害外周神经节的结构和功能。

Diabetic neuropathy（DN） is defined as the presence of symptoms and/or signs of peripheral nerve dysfunc-tion in people with diabetes.The aim of this study is to screen differentially expressed genes in peripheral ganglia in early stage type Ⅱ experimental diabetic rats.We compared gene expression profiles of peripheral ganglia in type Ⅱ diabetic and nondiabetic rats based on Illumina？ Sentrix？ BeadChip arrays.The results showed that 158 out of a total of 12 604 known genes were significantly differentially expressed,including 87 up-regulated and 71 down-regulated genes,in dia-betic rats compared with those in the nondiabetic rats.It is noted that some up-regulated genes are involved in the biological processes of neuronal cytoskeleton and motor proteins.In contrast,the down-regulated genes are associated with the re-sponse to virus／biotic stimulus／ other organism in diabetic rats.Kyoto Encyclopedia of Genes and Genomes（KEGG） analy-sis revealed that the most significant pathway enriched in the changed gene set is metabolism（P 0.001）.These results indicated that metabolic changes in peripheral ganglia of diabetic rats could be induced by hyperglycemia.Hyperglycemia could change the expression of genes involved in neuronal cytoskeleton and motor proteins through immune inflammatory response,and then impair the structure and function of the peripheral ganglia.