自发性2型糖尿病db/db小鼠肝病理损伤特点

Pathological characteristics of liver injury in spontaneous type 2 diabetic db/db mice

目的动态观察自发性2型糖尿病db/db小鼠肝产生的病理变化及特点,为将db/db小鼠肝作为2型糖尿病肝损伤模型的实验研究提供基础理论和实验依据。方法 7～8周龄,雄性,SPF级db/m小鼠作为对照组,糖尿病db/db小鼠作为模型组,各16只。动态观察其体重、空腹血糖(fasting blood glucose,FBG)、血清丙氨酸氨基转移酶(alanine aminotransferase,ALT)和天门冬氨酸氨基转移酶(aspartate aminotransferase,AST)活性,计算肝指数,光镜与电镜下观察肝的病理学改变。结果 db/db小鼠空腹血糖、血清ALT、AST活性均明显高于db/m小鼠,组织学检查发现db/db小鼠肝在16周龄时就出现严重损害,主要表现为肝细胞脂肪变性、炎细胞浸润等;到32周龄时病变加剧,镜下可见肝组织内有大量的胶原纤维;电镜下可见线粒体、内质网等结构被破坏甚至消失,出现明显的脂滴、炎细胞,组织内含有大量的胶原纤维。结论 db/db小鼠16周龄时肝出现明显的脂肪变性以及炎细胞浸润等,32周龄时表现为明显的纤维化,因此db/db小鼠的肝可作为实验研究时良好的2型糖尿病肝损伤模型。

Objective To dynamically observe the pathological changes and characteristics of the liver injury in spontaneous type 2 diabetic db/db mice,and to provide a theoretical and experimental basis for studies taking the liver of db/db mice as a model of type 2 diabetic liver injury.Methods db/m mice were used as the control group and diabetic db/db mice were used as the model group(male,7-8 weeks old,SPF grade)with 16 mice in each group.Weight,fasting blood glucose(FBG),serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)activity were dynamically observed,and the liver index was calculated.Pathological changes in the liver tissues were observed by light and electron microscopies.Results FBG,serum ALT and AST activity in the db/db mice were significantly higher than those in the db/m mice.Histological examination revealed that the liver of db/db mice was damaged severely at 16 weeks of age,including mainly hepatocyte steatosis and infiltration of inflammatory cells.By 32 weeks of age,the disease was intensified and there were massive deposit of collagen fibers in the liver tissue.Electron microscopy showed that mitochondria,endoplasmic reticulum,and other structures were destructed or even absent,and there were significant infiltration of inflammatory cells as well as fat droplets and massive deposit of collagen fibers in liver tissue.Conclusions The liver of db/db mice can be used as a good liver injury model of type 2 diabetes,displaying obvious steatosis and infiltration of inflammatory cells in 16-week-old mice and obvious fibrosis in 32-week-old mice.