药物干预对链脲佐菌素诱导的1型糖尿病大鼠心肌病变的影响

目的 探讨1型糖尿病大鼠心肌病理改变及阿司匹林、培哚普利、泼尼松对其心肌病变的影响.方法 30只SD大鼠随机分为糖尿病模型组(n=20)和正常对照组(n=10),糖尿病模型组一次性腹腔注射链脲佐菌素(STZ)60 mg/kg加枸橼酸钠溶液,正常对照组腹腔注射枸橼酸钠溶液.8周后观察2组大鼠的体重和平均血糖浓度.将建模的20只糖尿病大鼠随机分为4组(n=5),第4天起,分别给予生理盐水溶解的阿司匹林、培哚普利、泼尼松灌胃各5只,余5只和正常对照组每日以等体积生理盐水灌胃,共持续8周.8周后取各组大鼠心肌组织,HE染色,光镜和电镜下进行观察和比较.结果 大鼠以STZ注射后3 d血糖浓度≥16.7 mmol/L为造模成功,模型组20只大鼠全部成活,成模后大鼠出现明显多饮、多食、多尿和体重下降,HE染色显示糖尿病大鼠心肌细胞肿胀肥大、变性,核明显增大,心肌纤维断裂、溶解,收缩呈波浪状,排列紊乱,并有炎性细胞的浸润.电镜下可见糖尿病大鼠心肌肌纤维排列不规则,断裂溶解,肌纤维间糖原聚集,线粒体肿胀,线粒体大部分嵴不清晰,细胞间盘增宽.与糖尿病组相比,各药物干预组上述病理改变均有所减轻,而以培哚普利组最为明显.结论 STZ诱导的1型糖尿病大鼠模型制作方法成功率高,血糖值稳定,8周后出现明显的心肌病变,阿司匹林、培哚普利、泼尼松均能使糖尿病大鼠心肌病变有所减轻,以培哚普利最为有效.

Abstract：

Objective To investigate the pathological changes of myocardium in diabetic rats and the effect of aspirin, perindopril, prednisone on the pathological changes of myocardium in type 1 diabetic rats. Methods Thirty SD rats were randomly divided into the following groups: ( 1 ) diabetes mellitus (DM)group ( n = 20): treated with intraperitoneal injection of streptozocin (STZ) 60 mg/kg at one time, diluted in sodium citrate buffer. (2) normal control group (n = 10): intraperitoneal injection of sodium citrate buffer. The blood glucose and the weight were measured regularly for 8 weeks. The 20 diabetic model rats were randomly divided into four groups (n = 5 individually), from the 4th day, the rats were given normal saline dissolved aspirin, perindopril, prednisone gavage respectively, and the normal control group and diabetic group were given an equal volume of saline daily gavage. After 8 weeks, the pathological changes in the cardiac muscle tissue were observed under light microscope and electron microscope. Results Three days after the injection of STZ, the blood glucose in the DM group was higher than 16. 7 mmol/L,20 rats were all modeling successfully. The model rats suffered from polydipsia, polyphagia, polyuria and weight loss significantly. HE staining showed diabetic myocardial cell swell, hypertrophy, degeneration and significant nuclear enlargement; the myocardial fiber fractured,dissolved, contraction wavy and disorganized fibre infiltrated by inflammatory cells. Under electron microscope, diabetic myocardial muscle fibers arranged irregularly, fractured and dissolved; the glycogen between the muscle fiber accumulated, mitochondria swelled, most of the ridges in mitochondria were not clear, cell plate widened. Compared with the diabetic group, the above-mentioned pathological changes reduced in the drug intervention group,and the changes in perindopril group was most significant. Conclusion Injection of STZ 60 mg/kg could successfully induce diabetic in rats and held stable blood glucose level. After 8 weeks, diabetes could cause servere damages in myocardium in the rats, but aspirin, perindopril, prednisone could reduce the cardiomyopathy in diabetic rats,in which perindopril had more positive effect.

Impact of drug intervention on cardiomyopathy in STZ-induced type 1 diabetic rats

Objective To investigate the pathological changes of myocardium in diabetic rats and the effect of aspirin, perindopril, prednisone on the pathological changes of myocardium in type 1 diabetic rats. Methods Thirty SD rats were randomly divided into the following groups: ( 1 ) diabetes mellitus (DM)group ( n = 20): treated with intraperitoneal injection of streptozocin (STZ) 60 mg/kg at one time, diluted in sodium citrate buffer. (2) normal control group (n = 10): intraperitoneal injection of sodium citrate buffer. The blood glucose and the weight were measured regularly for 8 weeks. The 20 diabetic model rats were randomly divided into four groups (n = 5 individually), from the 4th day, the rats were given normal saline dissolved aspirin, perindopril, prednisone gavage respectively, and the normal control group and diabetic group were given an equal volume of saline daily gavage. After 8 weeks, the pathological changes in the cardiac muscle tissue were observed under light microscope and electron microscope. Results Three days after the injection of STZ, the blood glucose in the DM group was higher than 16. 7 mmol/L,20 rats were all modeling successfully. The model rats suffered from polydipsia, polyphagia, polyuria and weight loss significantly. HE staining showed diabetic myocardial cell swell, hypertrophy, degeneration and significant nuclear enlargement; the myocardial fiber fractured,dissolved, contraction wavy and disorganized fibre infiltrated by inflammatory cells. Under electron microscope, diabetic myocardial muscle fibers arranged irregularly, fractured and dissolved; the glycogen between the muscle fiber accumulated, mitochondria swelled, most of the ridges in mitochondria were not clear, cell plate widened. Compared with the diabetic group, the above-mentioned pathological changes reduced in the drug intervention group,and the changes in perindopril group was most significant. Conclusion Injection of STZ 60 mg/kg could successfully induce diabetic in rats and held stable blood glucose level. After 8 weeks, diabetes could cause servere damages in myocardium in the rats, but aspirin, perindopril, prednisone could reduce the cardiomyopathy in diabetic rats,in which perindopril had more positive effect.