不同浓度硝酸甘油对心脏缺血/再灌注的作用及ALDH2的作用

摘要

目的 探讨不同浓度硝酸甘油(GTN)对离体大鼠心脏缺血/再灌注损伤的作用,进一步分析线粒体乙醛脱氢酶2(ALDH2)在其中的作用.方法 采用离体大鼠心脏Langendorff灌流方法,局部结扎冠状动脉左前降支30 min,复灌30 min复制缺血/再灌注模型.实验分五组,正常对照组,单纯缺血/再灌注组,GTN低浓度组(10 -8 mol/L GTN),中浓度组(10-7 mol/L GTN)及高浓度组(2×10 -6 mol/L GTN).测定心室动力学指标和复灌期间冠脉流出液中乳酸脱氢酶( lactate dehydrogenase,LDH)含量,RT-PCR测定左心室前壁心尖组织线粒体ALDH2基因mRNA表达水平.结果 与单纯缺血/再灌注组相比,GTN低浓度组左心室发展压(LVDP)、室内压最大上升/下降速率(±dp/dtmax)均增高,左心室舒张末压(LVEDP)降低,中浓度组无明显差异,高浓度组LVDP和±dp/dtmax均降低；LVEDP增高.与缺血/再灌注组相比,正常对照组和低浓度GTN组心肌组织ALDH2 mRNA表达增高,中浓度无明显差异,高浓度组大鼠心肌ALDH2 mRNA表达降低.结论 低浓度GTN可对抗心肌缺血/再灌注损伤,高浓度GTN加重损伤,中浓度GTN对损伤影响不大,此现象可能与不同浓度GTN引起心肌ALDH2的释放量不同有关.%Objective To investigate the effects of different concentrations of nitroglycerin ( GTN) in isolated rat hearts subjected to ischemia and reperfusion (I/R) injury and the role of mitochondrial acetaldehyde dehydrogenase 2 ( ALDH2). Methods The isolated perfused rat hearts were subjected to 30 min local ischemia and 30 min reperfusion. The rats were divided into control, I/R, low concentration GTN (10~8 mol/L GTN) , middle concentration GTN (10~7 mol/L GTN) group, high concentration GTN (2 xlO"6 mol/L GTN) groups. The ventricular hemodynamic parameters and lactate dehydrogenase (LDH) release during reperfusion were measured. The ALDH2 mRNA expression of left anterior myocardium was detected by reverse transcriptase polymerase chain reaction (RT-PCR). Results Compared with those of I/R group, 10~8 mol/L GTN increased the levels of left ventricular developed pressure (LVDP) and maximal rise/fall rate of left ventricular pressure ( ± dP/dtmax) , decreased the level of left ventricular end-diastolic pressure ( LVEDP) ; 2 x 10 ~6 mol/L GTN decreased the levels of LVDP, ± dP/dtmax and increased the level of LVEDP. In contrast to that of I/R group, the expression of ALDH2 mRNA in control and 10 mol/L GTN groups were obviously increased; 10 mol/L GTN had no difference, while in 10-6 mol/L GTN group, the ALDH2 mRNA expression was decreased. Conclusions Low concentration of GTN reduces the degree of heart I/R injury; high concentration of GTN increases the I/R injury; middle concentration has no effect on the injury. The phenomenon is likely related to the release of AL-DH2.