不同浓度曲美他嗪对缺血/再灌注大鼠离体心脏的保护作用

目的 明确曲美他嗪在缺血再灌注（I/R）大鼠离体心脏损伤中的保护作用，并寻找最佳的药物浓度。 方法 选取体质量介于（220～250） g的雄性健康SD大鼠，适应性喂养1周后，快速腹腔注射水合氯醛（100 mg/ml）和肝素（500 U/kg）。离体心脏正常灌注开始后，实验随机分为5组，正常对照组，I/R组，5 μmol/L，10 μmol/L和20 μmol/L曲美他嗪处理I/R组。实验全程采用Labchart软件记录左心室内压力的数值，左心室发展压(LVDP)和左心室舒张末压(LVEDP)评价左心室的收缩功能。检测各组心脏释放的乳酸脱氢酶（LDH）的含量，观察心肌梗死面积的变化，检测各组心肌组织中半胱氨酸蛋白酶3（caspase-3）的活性、细胞色素（cytochrome）C和有活性的半胱氨酸蛋白酶3（cleaved caspase-3）的蛋白表达水平。 结果 和I/R组比较，5 μmol/L TMZ处理 I/R组LVDP有升高，左室舒张末压有降低趋势；而10 μmol/L TMZ处理I/R组和20 μmol/L TMZ处理I/R组均能够明显增加LVDP，显著降低左室舒张末压（P<0.05），但两组间比较无显著差异。和I/R组比较，5 μmol/L TMZ处理I/R组有降低心肌梗死面积、冠脉流出液中LDH的含量、caspase-3活性以及cytochrome c和cleaved caspase-3蛋白表达的趋势；而10 μmol/L TMZ处理I/R组和20 μmol/L TMZ处理I/R组均能够明显降低心肌梗死面积、冠脉流出液中LDH的含量、caspase-3活性以及cytochrome c和cleaved caspase-3的蛋白表达（P<0.05），但两组间比较无显著差异。 结论 10 μmol/L和20 μmol/L曲美他嗪在I/R离体心脏中具有保护作用。

Trimetazidine of different concentrations prevents ischemia/reperfusion injury in isolated rat heart

AIM To demonstrate the protective effect of trimetazidine against rat isolated heart ischemia /reperfusion(I/R) injury and to search for the optimal drug concentration. METHODS Male healthy SD rats weighing between 220g and 250 g were selected to feed adaptably for 1 week. The rats were rapidly intraperitoneally injected with chloral hydrate (100 mg/ml) and heparin (500 U/kg). After the normal perfusion of isolated heart, the rats were randomly divided into 5 groups: control group, I/R group, and respectively 5 μmol/L, 10 μmol/L and 20 μmol/L trimetazidine treatment with I/R group. The values of left ventricular pressure were recorded by Labchart software and left ventricular development pressure (LVDP) and left ventricular end-diastolic pressure (LVEDP) were used to evaluate the cardiac functions. The lactate dehydrogenase (LDH) content was detected, the myocardial infarction area was determined and the caspase-3 activity in the myocardial tissue of each group was detected. The protein levels of cytochrome c and cleaved caspase-3 were detected. These results were used as indicators to evaluate the degree of myocardial cell necrosis and apoptosis in each group. RESULTS Compared with that in the I/R group, I/R treatment in 5 μmol/L TMZ group showed an increase in LVDP and a decrease in LVEDP, but there was no statistical difference. Both I/R treatment in 10 μmol/L TMZ group and in 20 μmol/L TMZ group significantly increased LVDP and significantly reduced LVEDP, but there was no statistical difference between the two groups. Compared with that in the I/R group, I/R treatment in 5 μmol/L TMZ group showed a tendency to reduce myocardial infarction area, LDH content in coronary outflow, caspase-3 activity and cytochrome c and cleaved caspase-3 protein expressions, but there was no statistical difference. Both I/R treatment in 10 μmol/L TMZ group and in 20 μmol/L TMZ group significantly reduced the myocardial infarction area, LDH content in coronary outflow, caspase-3 activity and cytochrome c and cleaved caspase-3 protein expressions, but there was no statistical difference between the two groups. CONCLUSION This study confirms the protective effect of trimetazidine with 10 μmol/L and 20 μmol/L in isolated rat hearts I/R injury.