糖尿病肾病候选基因脂肪细胞蛋白酶时空表达变化的研究

目的利用基因芯片研究，笔者发现98个已知基因和31个已表达序列标志（EST）在2型糖尿病KK／Ta与正常对照BALB／c小鼠肾脏中存在着差异表达。为进一步筛选糖尿病肾病的遗传易感基因，有必要对差异表达基因脂肪细胞蛋白酶（Adipsin）的时空表达模式进行研究。方法分别于7、20、28和36周龄监测KK／Ta与BALB／c小鼠体重、血糖、尿白蛋白／肌酐比率以及肾脏病理改变；提取肾脏、心脏、肝脏、肺脏和脑组织中的总RNA，竞争性RT．PCR反应检测Adipsin基因的时空表达模式，并与尿白蛋白／肌酐比率进行相关性分析。结果Adipsin基因在小鼠。肾脏、心脏、肺脏以及脑组织中存在表达，在肝组织中无表达。20周龄糖尿病KK／Ta小鼠肾脏、心脏、肺脏中Adip—sin基因的表达量较BALB／c小鼠显著下调，在脑组织中的表达量无明显变化。随着KK／Ta小鼠周龄的增长及尿白蛋白排泄率的增加，Adipsin基因在肾脏中的表达逐渐下调，与尿白蛋白／肌酐比率呈负相关（r=-0．807，P〈0．05）。结论糖尿病状态下Adipsin基因在肾脏、心脏、肺脏中表达下调。肾组织中Adipsin基因的表达水平与尿白蛋白／肌酐比率密切相关，为糖尿病。肾病的可能易感基因。

The temporal and spatial expression patterns of adipsin, a candidate gene for diabetic nephropathy

Objective With a GeneChip expression analysis, 98 known genes and 31 expressed sequence tags （ESTs） were found to be differentially expressed between KK/Ta and BALB/c kidneys. To further screen the susceptibility genes for diabetic nephropathy, the temporal and spatial expression patterns of differentially expressed geue-adipsin were investigated. Methods The body weight, blood glucose, uri- nary albumin/creatinine ratio, and renal pathological changes of KK/Ta and BALB/c mice were measured at the 7, 20, 28 and 36 weeks of age. Total RNA was extracted from the kidney, heart, liver, lung, and brain. The temporal and spatial expression patterns of adipsin in diabetic KK/Ta mice were examined by competitive RT-PCR. The correlation analysis between adipsin expression and albuminuria level was carried out. Results The mRNA expression of adipsin was found in the kidney, heart, lung, and brain, but not in liver. The expression of adipsin in diabetic KK/Ta mice at 20 weeks of age was significantly down-regulated in kidney, heart, and lung than that in age-matched BALB/c mice, and unaltered in brain. Adipsin expres- sion in KK/Ta kidneys was significantly down-regulated with aging and negatively correlated to urinary albumin/ereatinine ratio （ r = -0. 807, P 〈 0. 05 ）. Conclusions The expression of adipsin mRNA was down- regulated in kidney, heart, and lung in diabetic state. Adipsin expression in KK/Ta kidneys was negatively correlated to urinary alhumin/creatinine ratio. It might he a candidate gene for diabetic nephropathy.