GLOMERULAR LESIONS IN NON-OBESE DIABETIC MICE

NOD小鼠自发地发展为胰岛素依赖型糖尿病（IDDM） 继发于免疫介导的胰腺β细胞破坏 小岛 这些小鼠表现出肾小球系膜基质数量的增加 在糖尿病发生之前， 肾小球硬化症”。在糖尿病出现后不久， 肾损害加重，包括系膜硬化， 肾小球基底膜增厚和蛋白尿。 形态计量学分析显示，肾脏重量和肾小球大小 与非糖尿病小鼠相比， 糖尿病小鼠肾小球体积/肾重量的比值升高。 我们通过竞争性PCR分离肾小球， 细胞外基质成分的周转。出现之前 IV型胶原mRNA的水平是糖尿病患者的3-4倍， 肾小球正常的SJL小鼠。此外，NOD小鼠还具有 肾小球比SJL少且大。因此， 应变具有发展硬化倾向而与糖尿病无关 其基础是基底细胞表达水平异常， 膜基因表达和肾小球数量减少。不久 在糖尿病发生后，我们发现 层粘连蛋白而不是胶原基因表达。这与一个 TGF-β 1基因表达的增加可能代表了 糖尿病肾病的早期分子事件我们还发现， 是晚期糖基化终产物在 糖尿病的早期症状

NOD mice spontaneously develop insulin-dependent diabetes mellitus (IDDM) secondary to immunologically-mediated beta cell destruction in pancreatic islets. These mice exhibit an increase in the amount of mesangial matrix before diabetes mellitus occurs and are therefore "prone to glomerulosclerosis". Shortly after the appearance of diabetes, there is an accentuation of the renal lesions consisting of mesangial sclerosis, thickening of glomerular basement membranes, and albuminuria. Morphometric analysis showed that the kidney weight and glomerular size were increased in diabetic mice, compared to non-diabetic mice, and that the ratio glomerular volume/kidney weight was elevated in diabetic mice. We explored by competitive PCR of isolated glomeruli the glomerular turnover of the extracellular matrix components. Prior to the appearance of diabetes the levels of type IV collagen mRNA were 3-4 times higher than in SJL mice who have normal glomeruli. In addition the NOD mice had fewer glomeruli than the SJL and those were larger. Therefore the NOD strain has a propensity to develop sclerosis irrespective of diabetes which is underlain by an abnormal level of expression of basement membrane gene expression and by a reduced number of glomeruli. Shortly after the occurrence of diabetes mellitus we found an upregulation of laminin but not collagen gene expression. This was associated with an increase in TGF-beta1 gene expression which may represent one of the early molecular events in diabetic nephropathy. We also found that there was accumulation of the advanced glycosylation end products in the kidneys shortly after the onset of diabetes.