GLOMERULAR LESIONS IN NON-OBESE DIABETIC MICE

NOD小鼠自发发展为胰岛素依赖型糖尿病(IDDM) 继发于免疫介导的胰岛β细胞破坏 小岛。这些小鼠表现出系膜基质数量的增加 在糖尿病发生之前，因此很容易发生 肾小球硬化“。糖尿病出现后不久， 肾损害加重，包括系膜硬化症， 肾小球基底膜增厚和蛋白尿。 形态计量学分析表明，肾脏重量和肾小球大小 在糖尿病小鼠中，与非糖尿病小鼠相比， 糖尿病小鼠肾小球体积/肾重比值升高。 我们用竞争性聚合酶链式反应对分离的肾小球进行了探索。 细胞外基质成分的周转。在亮相之前 糖尿病患者的IV型胶原基因水平是糖尿病患者的3-4倍 而不是肾小球正常的SJL小鼠。此外，NOD小鼠也有 肾小球较SJL少，且较大。因此，点头 压力有发展成硬化症的倾向，与糖尿病无关 它的基础是基底蛋白表达的异常水平 膜基因的表达和肾小球数量减少。很快就会 在糖尿病发生后，我们发现 层粘连蛋白，但不表达胶原基因。这与一个 转化生长因子-β1基因表达增加可能代表了 糖尿病肾病的早期分子事件。我们还发现在那里 是晚期糖基化终末产物在 糖尿病发作后不久的肾脏。

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.