目的 观察自发性2型糖尿病动物模型KKAy小鼠糖尿病早期肾损害的特征和演变,旨在探讨其在糖尿病肾病研究中的应用价值.方法 选择8周龄雄性KKAy小鼠和C57BL/6小鼠各20只,分别于8周龄、20周龄测定血糖、尿微量白蛋白、尿肌酐,并留取肾脏标本,于光镜及电镜下观察其肾脏病理特点.结果 不同周龄KKAy小鼠体质量、随机血糖均高于对照组C57BL/6小鼠(P<0.05).20周龄KKAy小鼠尿白蛋白排泄率显著高于8周龄KKAy小鼠和对照组C57BL/6小鼠(P<0.05).20周龄KKAy小鼠光镜下肾小球面积增大,肾小球毛细血管基底膜增厚,系膜基质增生,可见硬化结节;电镜下肾小球基底膜增厚,足突部分扁平、融合.结论 20周龄KKAy小鼠出现肥胖、高血糖、尿白蛋白排泄率增加及典型的糖尿病肾病病理改变,是研究2型糖尿病早期肾损害的理想动物模型.%Objective To investigate the early renal impairment in KKAy mice with spontaneous type 2 diabetes. Methods Blood glucose, urinary microalbumin and urinary creatinine of twenty male KKAy mice and twenty male C57BL/6 mice were measured at the age of 8,20 weeks respectively. The renal pathological changes were observed under light microscope and electron microscope. Results KKAy mice developed higher body weight and blood glucose than C57BL/6 mice at all the different ages (P ＜ 0.05 ). Urinary microalbumin/creatinine ratio in 20-week-age KKAy mice was higher than that in 8-week-age KKAy mice and C57BL/6 mice (P ＜ 0.05 ). Pathological lesions in 20-week-age KKAy mice were increasing of glomendar area, thickening of glomerular basement membrane, expansion of mesangial matrix,with sclerosis lesions under light microscope; thickening of basement membrane and fusion of foot processes were evident under electron mieroecope. Conclusion KKAy mice developed obesity, hyperglycemia, albuminuria and typical pathological lesions of diabetic nephropathy at 20 weeks of age. Therefore, KKAy mice may serve as a suitable model for the study of type 2 diabetes and early stage diabetic nephropathy in humans.
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