曲美他嗪对糖尿病心肌病干预的实验研究

Effect of trimetazidine on diabetic cardiomyopathy in rats

目的探讨曲美他嗪干预对糖尿病心肌纤维化及心肌微观结构的影响。方法健康雄性Wistar大鼠45只,随机分为2组:正常对照组(n=8)和实验组(n=37)。实验组予高脂高糖饮食,8周检测,出现胰岛素抵抗者腹腔注射STZ 20 mg/kg,1次/周,连续4周。正常对照组普通饮食,注射同体积的0.1 mol/L枸橼酸-枸橼酸钠缓冲液。继续喂养16周后,检测血糖≥16.7 mmol/L者为2型糖尿病大鼠,实验组大鼠随机分为糖尿病组(n=18)和曲美他嗪组(n=15)。曲美他嗪组大鼠以曲美他嗪15 mg/kg灌胃,1次/d,连续4周。同时,其他2组予同等量的蒸馏水灌胃。之后取血、处死,取室间隔心尖部福尔马林固定24 h,HE染色,免疫组织化学法检测Ⅰ、Ⅲ型胶原的阳性表达情况。透射电镜观察三组心肌组织微观结构。结果糖尿病组Ⅰ、Ⅲ型胶原表达的阳性率显著高于曲美他嗪组(P<0.05)。透射电镜显示糖尿病组心肌纤维断裂,细胞结构紊乱;曲美他嗪组心肌细胞结构基本正常,但仍有损伤。结论曲美他嗪通过对糖尿病心肌病心肌细胞代谢的影响,可以减轻心肌纤维化、改善心肌病理损伤及超微结构。

Objective To explore the effect of trimetazidine on myocardial fibrosis in diabetic cardiomyopathy rats.Methods Forty-five Wistar rats were randomized into two groups：normal control group（n=8）and experimental group（n=37）.The rats in experimental group were fed with high sugar-fat diet for 8 weeks to induce the insulin resistance,then were injected with STZ for 4 weeks.After that,the rats were fed for 16 weeks,and then the model rats of diabetic cardiomyopathy with FPG≥16.7 mmol/L were divided into two groups：DM group（n=18） and trimetazidine group（n=15）.The rats in trimetazidine group received trimetazidine for 4 weeks,while the rats received same volume of distilled water instead in the other two groups.Then all rats were killed.The interventricular septa were formalin-fixed,paraffin-imbedded and HE-stained.The microstructure of cardiac muscle was observed under transmission electron microscope（TEM）.Expression of collagen-Ⅰ and Ⅲ in the cardiac muscle was detected.All data were analyzed statistically.Results The positive expression of collagen-Ⅰand Ⅲ in DM group was significantly higher than in trimetazidine group.The microstructure of cardiac muscle in DM group was in great disorder,and cardiac muscle fibers were ruptured obviously.In trimetazidine group,the cardiac muscles were damaged slightly,and the microstructures were in normal order.Conclusion Trimetazidine can improve the pathological damages of cardiac muscle by influencing the myocardial energy metabolism of diabetic cardiomyopathy.