2 型糖尿病小鼠不同时间点的病理生理变化

Pathological and physiological changes of type 2 diabetic mice at different time points

摘要:

目的 检测不同时间点2 型糖尿病（T2DM）小鼠模型代谢指标、血清胰岛素、心功能等指标，明确T2DM 小鼠模型发生病理改变的时间。方法 雄性8 周C57BL/6 小鼠采用高脂联合链脲佐菌素（STZ）方法复制T2DM 动物模型，在STZ 注射不同时间点，罗氏血糖仪测量小鼠空腹血糖。用Elisa 试剂盒检测小鼠血清胰岛素，应用小动物超声检测小鼠左心室功能。苏木素- 伊红染色及Masson 染色观察心脏大小形态及心肌纤维化情况。结果 STZ 注射1 周后实验组小鼠空腹血糖升高，2 周后出现糖耐量和胰岛素耐量异常；8 周时，清胰岛素异常及左心室舒张功能障碍，并出现左心室肥厚和纤维化；12 周时出现左心室扩张，纤维化加重。结论 STZ 注射2 周小鼠空腹血糖升高，8 周时血清胰岛素降低，并发生左心室肥厚及舒张功能下降，12 周时左心室收缩功能下降，为研究T2DM 的发病机制及干预治疗提供了实验依据。

Abstract:

Objective To determine the time of pathological changes of type 2 diabetes mellitus mouse model by detecting serum insulin and the indexes of metabolism and cardiac function in type 2 diabetic mice at different time points. Methods Male 8-week C57BL/6 mice were used to establish the animal model of type 2 diabetes mellitus by high fat and low-dosage Streptozocin (STZ). At different time points after STZ injection, the fasting blood glucose in mouse tail artery was measured using the Roche glucometer. Serum insulin concentration was tested using mouse insulin ELISA kit. Small animal ultrasound was applied for detection of left ventricular function in the mice. Hematoxylin-eosin staining and Masson staining were used to observe the shape and size of the heart and myocardial fibrosis. Results In the experimental group, fasting blood glucose was significantly increased 1 week after STZ injection; glucose tolerance and insulin tolerance were impaired 2 weeks after STZ injection; at the 8th week, abnormal serum insulin and left ventricular diastolic dysfunction appeared and left ventricular hypertrophy and fibrosis were observed; at the 12th week, left ventricule was dilated, fibrosis was aggravated. Conclusions In the 2nd week after STZ injection, fasting blood glucose significantly increases; in the 8th week, serum insulin decreases, left ventricular hypertrophy and diastolic dysfunction appear; at th 12th week, there is left ventricular systolic dysfunction. This study provides an experimental basis for the study of the pathogenesis and treatment of type 2 diabetes mellitus.