摘要
目的研究2型糖尿病动物模型KKAy小鼠的糖尿病肝、肾的病变过程,探索KKAy小鼠作为2型糖尿病并发多脏器病变模型的价值。方法9~11周龄雄性KKAy小鼠(n=20)和对照组的雄性C57BL/J小鼠(n=25),测量14、16、20、24、28周龄小鼠空腹血糖和体重。两组动物分别于24、28周处死,测定血清肌酐、尿素;胆固醇、甘油三酯;丙氨酸氨基转移酶(ALT)、天门冬氨酸氨基转移酶(AST)。光镜观察两组小鼠肾脏、肝脏的病理改变。结果①KKAy小鼠体重、血糖比同龄对照组C57BL/J小鼠高(P<0.01)。②24、28周龄KKAy小鼠血脂均较对照组高(P<0.05);24周龄KKAy小鼠肌酐,ALT比对照组高(P<0.05);28周龄KKAy小鼠的肌酐、ALT及AST比对照组高(P<0.05)。③242、8周龄KKAy小鼠肾脏系膜基质增多,肾小管上皮细胞胞质出现明显空泡,肾间质有纤维化;肝脏结构紊乱,肝细胞胞质有明显空泡,肝细胞脂肪变。结论KKAy小鼠14周龄以后可出现明显肥胖,高血糖,24周龄、28周龄出现高脂血症,有肝、肾形态和功能的损害,是较好的研究2型糖尿病病变过程及并发症的动物模型。
Objective To study the changes of the liver and kidney in type 2 diabetic KKA^y mice and investigate the value of KKAy mice as a model of type 2 diabetes. Methods Twenty male KKAy mice and twenty-five male C57BL/J mice as controls were studied at 9 - 11 weeks of age. The fasting plasma glucose and weight were measured at 14, 16, 20, 24, 28 weeks of age. The mice were sacrificed at 24 and 28 weeks of age, respectively. Serum creatinine, urea, lipids, alanine aminotransferase （ALT） and aspartate aminotransferase （AST） were measured. The histology of renal and hepatic tissues was examined by light microscopy. Results 1. The KKAy mice developed obesity by 14 weeks of age （ P 〈 0.01 ）. 2. The KKAy mice developed hyperglycemia, hyperlipidemia at 24, 28 weeks of age （P 〈 0.05 ）, but there were no changes in the control group. The serum creatinine and ALT in KKAy mice were increased compared with those in the control group at 24 weeks of age （ P 〈 0.05）. The serum creatinine, ALT and AST in KKAy mice were increased compared with those in control group at 28 weeks of age （ P 〈 0.05）. 3. At 24 and 28 weeks of age, the increase of mesangial matrix was significant, and obvious vacuolization in the renal tubular epithelial cells and tubulointerstitial fibrosis were also observed. At the same time, the structure of liver was damaged, and significant fatty degeneration was present in the hepatocytes. Conclusion KKAy mice develop obesity, hyperglycemia after 14 weeks and develop hyperlipidemia at 24, 28 weeks of age, and there are hepatic and renal structural and functional damages. It is considered to be a good model for studying the pathological changes and complications of type 2 diabetes.
出处
《中国实验动物学报》
CAS
CSCD
2008年第4期241-243,F0002,共4页
Acta Laboratorium Animalis Scientia Sinica
基金
国家自然基金资助(编号:30672756和30572437)
北京市教委科技发展项目资助(编号:KM200610025012)
