2型糖尿病大鼠并发心肌病的研究

Study on cardiomyopathy complicated with type 2 diabetes mellitus in rats

目的 在大鼠中复制类似人类2型糖尿病模型,观察并发糖尿病性心肌病的情况.方法 取健康雄性SD大鼠120只,体质量180～220 g,按体质量及血糖值分为4组：（1）糖尿病组：40只,高糖高脂饲料喂养,一次性腹腔注射30 mg/kg链脲佐菌素（STZ）溶液 （2）STZ组：30只,普通饲料喂养,一次性腹腔注射30 mg/kg STZ溶液 （3）高糖高脂饲料组：25只,高糖高脂饲料喂养,一次性腹腔注射等容积柠檬酸盐缓冲液溶液 （4）对照组：25只,普通饲料喂养,一次性腹腔注射等容积柠檬酸盐缓冲液溶液.腹腔注射STZ溶液或柠檬酸盐缓冲液溶液后,观察动物饮水、进食及尿量变化.注射后4、8、12、16周,各组分批抽样检查,称取体质量,取血检测空腹血糖、空腹胰岛素、三酰甘油、总胆固醇 处死动物取心脏称质量,取心肌组织行光镜及透射电镜观察.结果 实验饲料喂养1周,各组大鼠体质量、血糖差异无统计学意义（P〉0.05） 喂养4周,STZ或柠檬酸盐缓冲液注射前,糖尿病组和高糖高脂饲料组大鼠体质量、空腹胰岛素、胰岛素抵抗指数较对照组和STZ组明显升高（P〈0.05） 糖尿病组与高糖高脂饲料组相比、STZ组和对照组相比差异均无统计学意义（P〉0.05）.注射后4个时段,糖尿病组和高糖高脂饲料组大鼠血糖、体质量、心脏质量、血三酰甘油、总胆固醇比同时段的对照组和STZ组增高（P〈0.05）,糖尿病组大鼠的上述指标较高糖高脂饲料组大鼠增加更显著,差异有统计学意义（P〈0.05）,STZ组和对照组相比差异无统计学意义（P〉0.05）.心肌光镜和电镜检查结果显示,糖尿病组大鼠心肌细胞肥厚并出现变性、凋亡等显著病变,间质胶原纤维增生 STZ组大鼠心肌无明显病理改变 高糖高脂饲料组大鼠心肌呈现类似糖尿病大鼠病理改变,但与糖尿病组大鼠相比,改变较不明显.结论 2型糖尿病大鼠成模4周后,心脏发生糖尿病性心肌病的病理改变,表现为心肌细胞肥大、变性,间质纤维组织增生,其发生率为100%.

Objective To study the development of cardiomyopathy complicated with type 2 diabetes mellitus in the rats. Methods The 120 health male Sprague-Dawley rats, weighing 180-220 g, were divided into 4 groups： （1）STZ-modeled diabetes, fed with high-carbohydrate plus high-fat diet （n=40） （2）fed with regular diet （n=30） （3）and （4）SD rats with citrate buffer instead of STZ injection, fed with high-carbohydrate and high fat diet （n= 25） and fed with regular diet （n= 25） At the 4th, 8 th, 12 th and 16 th week after the intra-peritoneal injection of STZ solution or citrate buffer solution, rats from each group were scarified and examined. Results There were no significant differences in body mass and blood glucose among those groups after one week of feeding （P〉0. 05）.After 4 weeks of feeding before injection, the body mass, fasting insulin （FINS） and insulin sensitive index （ISI） were obviously increased in diabetes group and high-carbohydrate plus high-fat control group as compared with STZ control group and normal control group （P〈 0. 05）. There were no significant differences between diabetes group and high-carbohydrate plus high-fat control group,between STZ control group and normal control group （P〉0. 05）. After injection, the blood glucose,body mass, ventricular mass, TG and TC were higher in diabetes group and high-carbohydrate plus high-lipid control group than in STZ control group and normal control group （P〈0.05）. The above parameters were much higher in diabetes group than in high-carbohydrate plus high-lipid control group, but there was no difference between STZ control group and normal control group （P〈0. 05）.Pathological examination showed that the weight of the heart was significantly increased, the myocardial cells were hypertrophied accompanying degenerative changes and apoptosis, the interstitial collagen fibers were hyperplasia in the diabetic rats. The ultrastructures also presented severe damage.These changes indicated that cardiomyopathy was induced in the diabetes rats. Although similar changes were found in the rats fed with high-carbohydrate plus high-fat diet, they were much less significant than those in the diabetic rats. Conclusions Cardiomyopathy developes frequently in the rats with type 2 diabetes mellitus induced by feeding high-carbohydrate plus high-lipid diet and single intra-peritonial injection of 30 mg/kg STZ solution.