一种建立小鼠2型糖尿病心肌病模型的方法

A method of establishing type 2 diabetic cardiomyopathy model in mice

目的:采用连续喂养高脂饮食(high-fat diet,HFD)结合单次腹腔注射链脲佐菌素(streptozotocin,STZ)的方法建立小鼠2型糖尿病心肌病模型。方法:将40只5~6周龄C57BL/6J雄性小鼠随机分成2组(每组各20只):对照(control)组,持续以普通饲料喂养;HFD+STZ组,持续以HFD喂养,并于造模第5周注射STZ(100mg/kg)。于造模实验开始(第0周)、第5周、第6周、第11周和第16周,测量体重和血糖,并于第11周和第16周分别对control组和HFD+STZ组小鼠进行心功能检测、胰岛素水平检测、组织学观察和心肌细胞凋亡分析。结果:造模过程中HFD+STZ组小鼠各时期的体重均大于control组(P<0.05),注射完STZ后小鼠体重略有下降,但仍高于control组。注射STZ 1周后,HFD+STZ组小鼠空腹血糖值均持续高于13.89 mmol/L。在造模第11周和16周时,HFD+STZ组小鼠胰岛素水平与control组相比均有降低(P<0.05)。心功能检测、组织学观察和心肌细胞凋亡分析显示,造模第11周时,HFD+STZ组小鼠的超声、心肌细胞面积和凋亡率等指标与control组相比变化不明显;造模第16周,HFD+STZ组小鼠出现心室功能障碍,心肌细胞肥大,心肌细胞的面积和心肌细胞凋亡率明显大于control组(P<0.05)。结论:采用连续喂养HFD结合单次注射STZ可成功建立小鼠2型糖尿病心肌病模型。

AIM:To establish a mouse model of type 2 diabetic cardiomyopathy induced by sustained high-fat diet(HFD)feeding and single intraperitoneal injection of streptozotocin(STZ).METHODS:The 5~6-week-old C57BL/6J mice were randomly divided into 2 groups(n=20 per group):the mice in control group received a sustained regular diet;the mice in HFD+STZ group received a sustained HFD and were intraperitoneally injected with STZ(100 mg/kg)at the 5th week.The body weight and blood glucose were measured at 0,5,6,11 and 16 weeks.The mice in control group and HFD+STZ group were analyzed with echocardiography,HE staining,ELISA and immunohistochemistry at the 11th and 16th weeks.RESULTS:The body weight of the mice in HFD+STZ group was higher than that in control group(P<0.05)during each modeling period,and was slightly decreased 1 week after STZ injection.The blood glucose of the mice in HFD+STZ group was higher than 13.89 mmol/L 1 week after STZ injection.The serum insulin of the mice in HFD+STZ group was lower than that in control group(P<0.05)at the 11th week and the 16th week.Echocardiography,HE staining and immunohistochemistry analysis showed that the mice in HFD+STZ group had mild ventricular dysfunction and cardiomyocyte hypertrophy,and cardiomyocyte area and apoptosis rate were obvious higher than those in control group(P<0.05)at the 16th week,while these indicators were not obviously changed in HFD+STZ group compared with control group at the 11th week.CONCLUSION:The sustained HFD feeding and single intraperitoneal injection of STZ successfully establish a mouse model of type 2 diabetic cardiomyopathy.