Schrijvers Bieke F, De Vriese An S, Van de Voorde Johan, Rasch Ruth, Lameire Norbert H, Flyvbjerg Allan
Medical Research Laboratories, Institute of Experimental Clinical Research, Aarhus University Hospital, Denmark.
Nephrol Dial Transplant. 2004 May;19(5):1092-7. doi: 10.1093/ndt/gfh107. Epub 2004 Feb 19.
Type 2 diabetes has become the single most frequent cause of end-stage renal disease. The Goto-Kakizaki rat is currently used as a model for lean type 2 diabetes, but its renal changes have not been fully characterized. We investigated long-term functional and structural renal changes in the Goto-Kakizaki rat to evaluate if this animal model resembles the changes observed in human diabetic kidney disease.
Urinary albumin excretion, creatinine clearance and blood pressure were measured at the age of 2, 8 and 14 months in 12 female Goto-Kakizaki rats and 10 female, non-diabetic Wistar rats. To study kidney morphology, kidney weight, glomerular volume, basement membrane thickness, mesangial fraction and total mesangial volume were determined at 14 months.
Urinary albumin excretion rose progressively over time in both groups, but was significantly higher in Goto-Kakizaki rats than in Wistar rats. Creatinine clearance decreased over time in Goto-Kakizaki rats but not in Wistar rats. Blood pressure was in the normotensive range in all animals throughout the study. Kidney weight, glomerular volume, basement membrane thickness, mesangial fraction and total mesangial volume were significantly higher in Goto-Kakizaki rats than in Wistar rats. Body weight and blood glucose levels were higher, whereas serum insulin levels were not different or lower in Goto-Kakizaki rats compared with Wistar rats.
The Goto-Kakizaki rat is a lean, hyperglycaemic, euinsulinaemic, normotensive experimental model of type 2 diabetes with robust functional and structural renal changes.
2型糖尿病已成为终末期肾病最常见的单一病因。目前，Goto-Kakizaki大鼠被用作瘦型2型糖尿病的模型，但其肾脏变化尚未得到充分表征。我们研究了Goto-Kakizaki大鼠长期的肾脏功能和结构变化，以评估该动物模型是否与人类糖尿病肾病中观察到的变化相似。
对12只雌性Goto-Kakizaki大鼠和10只雌性非糖尿病Wistar大鼠在2、8和14月龄时测量尿白蛋白排泄量、肌酐清除率和血压。为研究肾脏形态，在14月龄时测定肾脏重量、肾小球体积、基底膜厚度、系膜分数和系膜总体积。
两组大鼠的尿白蛋白排泄量均随时间逐渐升高，但Goto-Kakizaki大鼠显著高于Wistar大鼠。Goto-Kakizaki大鼠的肌酐清除率随时间下降，而Wistar大鼠则无此变化。在整个研究过程中，所有动物的血压均在正常范围内。Goto-Kakizaki大鼠的肾脏重量、肾小球体积、基底膜厚度、系膜分数和系膜总体积均显著高于Wistar大鼠。与Wistar大鼠相比，Goto-Kakizaki大鼠的体重和血糖水平更高，而血清胰岛素水平无差异或更低。
Goto-Kakizaki大鼠是一种瘦型、高血糖、正常胰岛素水平、血压正常的2型糖尿病实验模型，具有明显的肾脏功能和结构变化。
