自发性2型糖尿病KK/Ta小鼠肾脏基因表达谱的研究  

Gene Expression Profile in Spontaneous Type 2 Diabetic KK/Ta Mice

作　　者：范秋灵[1] 董雪竹[1] 王娟[1] 杨爽[1] 陈莹[1] 姜奕[1] 王力宁[1] 

机构地区：[1]中国医科大学附属第一医院肾内科,沈阳110001

出　　处：《中国中西医结合肾病杂志》2012年第3期213-218,I0004,共7页Chinese Journal of Integrated Traditional and Western Nephrology

基　　金：国家自然科学基金资助项目(No.30700369);教育部留学回国人员科研启动基金资助项目(No.教外司留[2006]331号);辽宁省教育厅高校科研计划项目(No.L2010658);沈阳市科技计划项目(No.F11-264-1-38)

摘　　要：目的:应用基因芯片技术研究自发性2型糖尿病KK/Ta小鼠肾脏基因表达谱,旨在寻找糖尿病肾病的易感基因。方法:提取20周龄雄性KK/Ta(n=3)和BALB/c(n=2)小鼠肾脏总RNA,应用Affymetrix公司生产的Affymetrix Murine Genome U74Av2基因芯片检测肾脏基因表达谱。选择差异表达基因,通过竞争性RT-PCR反应验证基因芯片的结果。结果:98个已知基因和31个表达序列标签(ESTs)在20周龄KK/Ta与BALB/c小鼠的肾脏中存在着差异表达。与BALB/c小鼠相比,KK/Ta小鼠肾脏中21个已知基因和7个EST表达上调,77个已知基因和24个EST表达下调。竞争性RT-PCR反应确认了基因芯片研究的结果。结论:KK/Ta小鼠肾脏中的差异表达基因广泛参与细胞外基质的合成与降解、信号传导、转录调节与蛋白质合成、离子转运、葡萄糖与脂类代谢等。糖尿病肾病易感基因位点UA-1区域的差异表达基因S-腺苷高同型半胱氨酸水解酶基因Ahcy为糖尿病肾病的可能易感基因。Objective：To identify susceptibility genes for diabetic nephropathy,GeneChip Expression Analysis was employed to survey the gene expression profile of diabetic KK/Ta mouse kidneys.Methods：Kidneys from three KK/Ta and two BALB/c mice at 20 weeks of age were dissected.Total RNA was extracted and labeled for hybridizing to the Affymetrix Murine Genome U74Av2 array.The gene expression profile was compared between KK/Ta and BALB/c mice using GeneChip expression analysis software.Competitive RT-PCR was used to confirm the results of GeneChip for a selected number of genes.Results：Out of 12,490 probe pairs present on GeneChip,98 known genes and 31 expressed sequence tags（ESTs） were found to be differentially expressed between KK/Ta and BALB/c kidneys.Twenty-one known genes and 7 expressed sequence tags（ESTs） that increased in expression and 77 known genes and 24 ESTs that decreased in KK/Ta kidneys were identified.These genes are related to renal function,extracellular matrix expansion and degradation,signal transduction,transcription regulation,ion transport,glucose and lipid metabolism,and protein synthesis and degradation.Conclusion：The gene expression profile in KK/Ta kidneys is different from that in age-matched BALB/c kidneys.Altered gene expression of S-adenosylhomocysteine hydrolase（Ahcy） in the vicinity of UA-1 may be responsible for the development of albuminuria in diabetic KK/Ta mice.

关 键 词：糖尿病肾病 KK/Ta小鼠 基因芯片 易感基因 S-腺苷高同型半胱氨酸水解酶基因 

分 类 号：R587.1[医药卫生—内分泌]