GLOMERULAR LESIONS IN NON-OBESE DIABETIC MICE

非肥胖糖尿病小鼠的肾小球病变

• 批准号: 3855331
• 负责人: L J STRIKER
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3855331
• 关键词: albuminuria; basement membrane; collagen; diabetic nephropathy; disease /disorder model; extracellular matrix proteins; gene induction /repression; heparan sulfate; insulin dependent diabetes mellitus; kidney cell; laboratory mouse; laminin; messenger RNA; nephrosclerosis; proteoglycan; renal glomerulus; streptozotocin

NOD mice spontaneously develop insulin-dependent diabetes mellitus (IDDM) secondary to immunologically-mediated beta cell destruction in pancreatic islets. Shortly after the appearance of diabetes, NOD mice developed renal lesions consisting of diffuse mesangial sclerosis, thickening of glomerular basement membranes, and the development of albuminuria. These lesions closely mimic those of IDDM in humans. Morphometric analysis showed that the kidney weight and glomerular size were increased in diabetic mice compared to non-diabetic mice, and further, that the ratio glomerular volume/kidney weight was also elevated in diabetic mice. These findings suggest that this disproportionate increase in glomerular size may play an important role in the development of diabetic nephropathy. Preliminary analyses of mRNA levels of matrix proteins, assessed by the RNase protection assay, reveal relative increases in alpha1 type IV collagen, laminin B1, and heparan sulphate proteoglycan. Finally, since the onset of diabetes is variable in NOD mice, we have begun experiments in which we have synchronized the induction of diabetes by the injection of streptozotocin.

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 在糖尿病出现后不久，NOD小鼠的肾脏 病变包括弥漫性系膜硬化、肾小球增厚 基底膜和蛋白尿的发展。 这些病变 与人类的胰岛素依赖型糖尿病相似。 形态计量学分析表明， 糖尿病小鼠肾脏重量和肾小球体积增加 与非糖尿病小鼠相比， 在糖尿病小鼠中体积/肾重也升高。 这些发现 这表明肾小球大小不成比例增加可能在 糖尿病肾病的早期症状有哪些？ 初步 通过RNase评估的基质蛋白的mRNA水平分析 保护试验，揭示了α 1 IV型胶原蛋白的相对增加， 层粘连蛋白B1和硫酸乙酰肝素蛋白聚糖。 最后，自从 糖尿病在NOD小鼠中是可变的，我们已经开始了实验， 已经同步通过注射 链脲佐菌素