自发性2型糖尿病大鼠肾脏组织学增龄性的研究

Study on the aging-related changes in renal histomorphology in Goto-Kakizaki rats

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。测血糖、UAlb等指标。取肾脏,进行大体、光镜、电镜观察。结果 GK大鼠血糖随周龄增加而增高(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大鼠血糖在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。

Objective To study the aging-related changes in renal histomorphology in Goto-Kakizaki （GK） rats. Methods Thirty GK male rats were divided into 4-, 12- and 20-week old groups（n=10, each） 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 ageing （P〈0. 01）, the concentration of total urinary protein also increased with ageing （P 〈0. 01）, and the renal weight , length , and thickness of parenchyma and cortex increased with ageing （P 〈0.01）. Optical microscopy revealed the localized glomerular hyalinization, sclerosis, atrophy, increased thickness of walls of glomerular and interstitial vessels, and luminal stenosis in the GK rats. The circumference of the glomerula in 4-week GK rats was longer than in the aged, as compared to Wistar rats （P=0. 01）. Eleetmnmicmscopy revealed atrophy and hypofunction of the some podocytes, which was getting Worse with aging. Conclusion Hyperglycemia has oceured in the GK rats aged 4 weeks. There exists the typical pathologic changes of kidney in the early stage. The impairment deteriorates with the disease prolonging. GK rat is an ideal animal model for studying kidney impairment of T2DM.