糖尿病合并冠心病 ZDF 大鼠模型的构建

摘要

目的：构建Ⅱ型糖尿病合并冠心病的大鼠模型。方法采用高脂饲料喂养结合连续注射盐酸异丙肾上腺素（ ISO）制备Ⅱ型糖尿病合并冠心病的Zucker糖尿病肥胖大鼠（ Zucker diabetic fatty， ZDF）模型。通过血清肌酸激酶（ CK）、血清肌酸激酶同工酶（ CK-MB）、心电图ST波及心脏组织形态评价模型。结果非DM模型组和DM-CHD组随给药次数增多CK表达逐渐升高，CK-MB表达先升高后下降，说明大鼠心肌损伤已形成。模型大鼠心电图II导联ST段的偏移表明心肌损伤已经形成。注射模型组大鼠心肌病理切片结果显示空白对照组大鼠心肌细胞正常，ZDF大鼠在被连续注射5 d ISO后心肌坏死面积达到心肌截面的1／2，10 d后心肌坏死面积达到心肌截面的3／4。结论 CK、CK-MB含量变化、心电图ST波变化和心肌病理切片显示造模已成功。 ISO能造成一定程度的心肌损伤，可采用连续注射ISO进行冠心病模型的构建。本文建立了一种简便的采用高脂饲料喂养结合连续注射ISO的糖尿病合并冠心病大鼠模型的构建方法。%Objective The purpose of the present study was to develop an animal model of type II diabetic coro-nary heart disease in Zuker diabetic fatty ( ZDF) rats.Methods The ZDF rat model of type II diabetic coronary heart disease was prepared by high-fat diet feeding combined with continuous injection of isoprenaline hydrochloride (ISO) in a dose of 1 mg· mL-1 for 10 consecutive days.Serum creatine kinase (CK), and creatine kinase izozyme (CK-MB), ST segment in electrocardiogram ( ECG) and myocardial pathological changes were detected to evaluate the rat model.Results CK of both the control and model groups was gradually increased with ISO injections, while CK-MB increased first and then decreased.The ST segment in ECG part II had significant changes.The pathological examination found that about half of the myocardial cross section in the model group was necrotic after injections of ISO for 5 days and more than 3/4 of the my-ocardial cross section was necrotic after injection of ISO for 10 days.The results indicated that ISO caused myocardial inju-ry in ZDF rats.Conclusions The variation of CK-MB, CK, ST segments in ECG and myocardial necrosis indicate that the model is successfully established.The use of high-fat diet combined with continuous injection of isoprenaline hydrochlo-ride in a dose of 1 mg· mL is a simple way to develop a Zuker diabetic fatty rat model of type II diabetic coronary heart dis-ease.