卡托普利对实验性2型糖尿病心肌病大鼠模型心脏保护作用

Protective effects of captopril on cardiac function and structure in experimental type 2 diabetic cardiomyopathy rat model

目的研究卡托普利对实验性2型糖尿病心肌病(T2DC)模型动物心脏保护作用和可能机制。方法以高糖脂饲料负荷30 mg/kg剂量链脲佐菌素一次性腹腔注射建立T2DC大鼠模型,观察卡托普利45 mg/kg灌胃给药6周对模型动物血糖和血脂水平,心脏功能和结构变化,心肌脂肪酸含量以及心肌组织过氧化物增殖体激活受体α(PPARα)和葡萄糖转运体4(GLUT4)基因表达等指标的影响。结果与T2DC大鼠模型比较,卡托普利给药后,左心室收缩压、左心室最大收缩速率、左心室最大舒张速率的绝对值和心输出量分别显著增加15%、77%、52%和54%(P<0.05或P<0.01);室间隔厚度降低40%(P<0.001);血浆糖化血红蛋白和心肌组织游离脂肪酸含量分别降低31%和24%(P<0.01,P<0.05);心肌组织PPARα基因表达显著降低(P<0.05),GLUT4基因表达显著增加(P<0.05)。结论卡托普利可以显著改善T2DC模型动物心脏功能、抑制心室重构,其作用机制可能同调节与能量代谢相关基因表达、减轻心脏内脂肪积聚有关。

Objective To study effects of captopril on cardiac function and structure in the experimental type 2 diabetic cardiomyopathy （T2DC） rat model. Methods The experimental type 2 DC model rats were induced by feeding with high sucrose-fat diet and intraperitoneal （i. p. ） injection with 30 mg/kg of streptozotocin. The model rats were intragastric given with captopril at the dose of 45 mg/kg for six months totally. At the thirteenth week, the parameters of cardiac output （CO）, left ventricular systolic pressure （LVSP）, left ventricular end diastolic pressure （LVEDP） , the maximum rate of myocardial contraction （ ＋ dp/dtmax） and the maximum rate of myocardial diastole （ - dp/dtmax） weredetected using MP150 polygraph physiological signal recorder to evaluate cardiac function. The thickness of interventricular septal （IST） and left ventricular wall （LVWT） was measured to assess cardiac structure. Levels of fasting blood sugar （ i. e., fasting plasma glucose （FPG） and glycated hemoglobin Alo （HbAlo））, blood lipid （i. e., total cholesterol （TC） and triglyceride （TG）） and myocardial non-esterified fatty acids （NEFA） and creatine kinase （CK） were determined by ultraviolet spectrophtometric method. The genes expression of cardiac peroxisome proliferator activated receptor-et （PPAR ct） and glucose transporter-4 （GLUT4） mRNA were detected by real-time PCR method. Results When compared with the drug-untreated T2DC rat model, the parameters of LVSP, ＋ dp/dt absolute value of -dp/dtmix and CO were significantly increased by 15% , 77% , 52% and 54% , respectively, after treated with 45 mg/kg of captopfil. Meanwhile, the value of IST was decreased by 40% after treatment of captopril in T2DC rats. Levels of plasma HbAlo and myocardial NEFA were remarkably decreased by 31% and 24% , when compared with T2DC group. Furthermore, expression of PPAR ot was significantly decreased while GLUT4 mRNA increased, when compared with drug-untreated model rats. Conclusion Captopril treatment could effectively attenuate the diastolic and systolic dysfunction and inhibit the cardiac hypertrophy in experimental type 2 diabetic cardiomyopathy rats, and the therapeutic mechanism might be relate to mediating energy metabolism and lowering lipid accumulation in the heart.