【摘要】 目的 了解自发性糖尿病(GK)大鼠肾脏组织学的增龄性特点，以及病变进展的变化规律。 方法 4周龄、12周龄、20周龄雄性GK大鼠各10只。周龄匹配的雄性Wistar大鼠30只为对照组。测BG、UAlb等指标。取肾脏，进行大体、光镜、电镜观察。 结果 GK大鼠BG随周龄增加而增高(P<0.01)，GK大鼠尿总蛋白浓度随周龄增加而增高(P<0.01);GK大鼠肾重量、肾长径、肾实质及肾皮质厚度随周龄增加而增加(P<0.01);光镜下随周龄增加肾小球逐渐出现局灶性玻璃样变，继之发生硬化、萎缩，肾小球血管及肾间质血管壁增厚、管腔闭塞等病理改变;4周龄GK大鼠的肾小球平均周长大于同周龄Wistar大鼠 (P =0.01);电镜下大鼠肾脏的亚细胞结构出现萎缩及功能减退，并随着大鼠周龄的增加而加重。 结论 GK大鼠BG在4周龄已出现升高，之后在高水平延续，早期即出现典型的肾损害病理学变化，且随病程延长而加重。GK大鼠是研究T2DM肾损害的理想模型。

　　关键词：自发性糖尿病大鼠;肾;糖尿病，2型;增龄

　　Study on the renal histomorphological changes with age of Goto-Kakizaki rats MA Fang, CANG Yan-qin, LI Qian-yu, et al. Shanghai the 10th People’s Hospital, School of Medicine, Tongji University, Shanghai 200072, China; Changhai Hospital, the 2nd Military Medical University, Shanghai 200433, China

　　Corresponding author: Zhao Bao-zhen, e-mail: baozhenzhao@hotmail.com

　　【Abstract】Objective To study the renal histomorphological changes with age of Goto-Kakizaki (GK) rats. Methods Thirty GK male rats were divided into 4-, 12- and 20-week groups (n=10) according to their age. Thirty age-matched Wistar male rats were used as the control. The indices concerning blood glucose, urinary protein, etc. were measured. Their kidneys were studied with gross, optical mocroscope, and electronmicroscope observations. Results The level of blood glucose of GK rats increased with age (P<0.01), the concentration of total urinary protein also increased with age (P<0.01), and the renal weight , length , and thickness of parenchyma and cortex increased with age (P<0.01). Optical microscopy revealed localized glomerular hyalinization, and then sclerosis, atrophy, increased thickness of walls of glomerular and interstitial vessels, and luminal stenosis as well in the GK rats with the age growing. The circumference of the glomerula in 4-week GK rats was longer than that in the corresponding Wistar rats (P=0.01). Electronmicroscopy revealed atrophy and hypofunction of the some podocytes, and the condition of which was getting worse with the age growing. Conclusions Hyperglycosemia has occured in the GK rats aged 4 weeks. There exists the typical pathologic changes of kidney impairment in the early stage. The impairment deteriorates with the disease prolonging. GK rat is an ideal animal model for studying kidney impairment of T2DM.

　　【Key Words】 Goto-Kakizaki (GK) rats; Kidney; Diabetes mellitus, type 2; Morphological changes with the age growing