Sato Nahoko, Komatsu Koji, Kurumatani Hajimu
Pharmaceutical Research Laboratories, Toray Industries, Inc., Kamakura, Kanagawa, Japan.
Am J Nephrol. 2003 Sep-Oct;23(5):334-42. doi: 10.1159/000072915. Epub 2003 Aug 13.
BACKGROUND/AIM: Prolonged exposure to hyperglycemia is one of the key factors to induce progressive diabetic nephropathy in humans. We examined whether or not the same phenomenon is observed in a nonobese type 2 diabetes model, in Goto-Kakizaki (GK) rats.
Urine and serum samples from GK and Wistar rats were collected to measure biochemical parameters of the renal function. The kidneys of these animals were histopathologically and immunohistochemically analyzed.
Moderate hyperglycemia was sustained in GK rats during the experimental period. Noticeable morphological changes in the kidneys such as segmental glomerulosclerosis and tubulointerstitial fibrosis were observed only at 24 months of age. The expression of alpha smooth muscle actin and type IV collagen in glomeruli and tubulointerstitium was increased at 12 months of age and later. The macrophage infiltration was increased in parallel with the progression of renal lesions. The excretion of urinary protein in GK rats was increased only at 24 months of age. Moreover, the functional and morphological changes in Wistar rats were less severe than in age-matched GK rats.
We conclude that renal changes of GK rats at a late stage were similar to those of progressive human diabetic nephropathy and that prolonged hyperglycemia may play a more crucial role in inducing progressive diabetic nephropathy than aging and obesity.
背景/目的：长期暴露于高血糖状态是导致人类糖尿病肾病进展的关键因素之一。我们研究了在非肥胖型2型糖尿病模型即Goto-Kakizaki（GK）大鼠中是否也会出现同样的现象。
收集GK大鼠和Wistar大鼠的尿液和血清样本，以检测肾功能的生化指标。对这些动物的肾脏进行组织病理学和免疫组织化学分析。
在实验期间，GK大鼠维持中度高血糖状态。仅在24月龄时观察到肾脏出现明显的形态学变化，如节段性肾小球硬化和肾小管间质纤维化。在12月龄及之后，肾小球和肾小管间质中α平滑肌肌动蛋白和IV型胶原的表达增加。巨噬细胞浸润随着肾脏病变的进展而增加。GK大鼠仅在24月龄时尿蛋白排泄增加。此外，Wistar大鼠的功能和形态学变化比年龄匹配的GK大鼠轻。
我们得出结论，GK大鼠晚期的肾脏变化与人类进行性糖尿病肾病的变化相似，并且长期高血糖在诱发进行性糖尿病肾病方面可能比衰老和肥胖发挥更关键的作用。
