自发性2型糖尿病KKAy小鼠心脏结构和功能改变实验研究

Changes in cardiac structure and function of spontaneously type 2 diabetic KKAy mice

目的观察自发性2型糖尿病KKAy小鼠心脏结构和功能的改变及进展,评估其是否为糖尿病心肌病模型,为后续药效实验的开展提供依据。方法取12周龄雄性KKAy小鼠24只作为模型组,取24只C57BL/6J小鼠作为对照组,分别于14,18,22,26周龄按随机原则各组处死6只,测量2组小鼠体重、空腹血糖和心脏功能学指标,HE染色、Masson染色观察2组小鼠心脏病理改变。结果不同周龄模型组小鼠的体重、空腹血糖水平、舒张期左室前壁厚度(LVAWd)和舒张期左室后壁厚度(LVPWd)均明显高于同期对照组(P均<0.05)。不同周龄模型组小鼠的二尖瓣口血流多普勒E/A、二尖瓣环组织多普勒e’/a’均明显低于同期对照组(P均<0.05),且随周龄增长逐渐降低;而E/e’均明显高于同期对照组(P均<0.05),且随周龄增长逐渐增高;2组小鼠各周龄的左心室射血分数(LVEF)比较差异均无统计学意义(P均>0.05),均在正常范围内。心脏组织病理形态学可见模型组心肌细胞排列紊乱、细胞肥大、空泡样变和心肌细胞纤维化,且心肌间质及血管周围胶原纤维的面积均明显大于对照组(P均<0.05)。结论KKAy小鼠在高脂饮食喂养后血糖持续升高,且心室室壁厚度稳定增加,伴持续性心肌纤维化及心脏舒张功能障碍等特征,符合糖尿病心肌病的发病特征,是较为稳定的糖尿病心肌病模型。

Objective It is to observe the changes and progress of cardiac structure and function in spontaneous type 2 diabetes mellitus KKAy mice,to evaluate whether it is a diabetic cardiomyopathy(DCM)model,and to provide evidence for further pharmacodynamic experiments.Methods Twenty-four 12-week-old male KKAy mice were taken as the model group and 24 C57BL/6J mice were taken as the control group,in which 6 mice were sacrificed at 14,18,22 and 26 weeks of age according to the random principle,and their body weight,fasting blood glucose and cardiac functional indexes were measured,their cardiac pathological changes were observed by HE staining and Masson staining.Results The body weight,fasting blood glucose,left ventricular anterior wall depth(LVAWd)and left ventricular posterior wall depth(LVPWd)of the mice in the model group were significantly higher than those of the control group at the same age(all P<0.05).The mitral orifice blood flow Doppler E/A and mitral annular tissue Doppler e’/a’of the mice in the model group were significantly lower than those of the control group at the same age(all P<0.05),and gradually decreased with age increasing,while E/e’was significantly higher than that of the control group(P<0.05),and gradually increased with age increasing.The differences in left ventricular ejection fraction(LVEF)of the mice at each week of age were not statistically significant between the 2 groups(all P>0.05),and were in the normal range.The cardiac histopathological examination showed that there were disordered arrangement of cardiomyocytes,cell hypertrophy,vacuolar degeneration and myocardial fibrosis in the model group,the myocardial mesenchyme and peripheral vessel fibrotic area were significantly bigger than the control group(P<0.05).Conclusion After the high-fat diet,the blood glucose of KKAy mice continued to rise,and the ventricular wall depth increased steadily,accompanied by persistent myocardial fibrosis and cardiac diastolic dysfunction.It was consistent with the characteristics of DCM and was a relatively stable DCM model.