缺血预处理减轻在体家兔心肌细胞凋亡

Ischemic preconditioning reduces cardiomyocytic apoptosis in rabbit heart in vivo

在麻醉家兔心肌缺血 再灌注 (ischemia reperfusion ,IR)模型上 ,观察IR和缺血预处理 (ischemicprecon ditioning ,IP)对血流动力学、心外膜电图、心肌梗塞范围、心肌细胞凋亡和凋亡相关调控基因蛋白 (Fas、Bcl 2、Bax等 )的影响。所得结果如下 :(1)在IR过程中 ,动脉血压、心率和心肌耗氧量进行性降低 ;心外膜电图ST段在缺血期明显抬高 (P <0 0 0 1) ,再灌注时逐渐恢复至基础对照值。 (2 )单纯IR组的梗塞心肌占缺血心肌的 5 7 7±2 0 % ,IP组的梗塞心肌为 2 7 7± 1 5 % (P <0 0 1)。 (3)凝胶电泳显示 ,单纯IR组的缺血组织DNA呈云梯状 ,IP组则无明显云梯状 ;原位末端标记表明 ,IP组缺血未坏死心肌的凋亡细胞较IR组稀少 ;流式细胞术测得IR和IP组中缺血心肌的细胞凋亡率分别为 11 2± 0 4%和 6 35± 0 2 % (P <0 0 1)。 (4)与非缺血心肌相比 ,IR和IP组缺血心肌的Fas和Bax蛋白表达均明显增高 (P <0 0 5 ) ,且IR组的Fas蛋白表达较IP组的明显 (P <0 0 5 )。IR组缺血心肌Bcl 2 /Bax较非缺血心肌组织明显减小 (P <0 0 1)。以上结果表明 ,IP减少IR引发的心肌细胞凋亡 ,并减少IR心肌组织中Fas蛋白的表达。

The effects of ischemia reperfusion (IR) and ischemic preconditioning (IP) on hemodynamics, epicardial electrography, myocardial infarct size, cardiomyocytic apoptosis and gene proteins involving apoptosis (Fas, Bcl 2 and Bax) were observed in aneasthetized rabbit myocardium. The results are as follows. (1) During ischemia reperfusion, heart rate, arterial blood pressure and myocardial oxygen consumption were reduced progressively. The epicardial electrographic ST segment was elevated significantly during ischemia (P<0 001)and recovered to the baseline during reperfusion. (2) The infarct size occupied 57 7±2 0% of the ischemic myocardium in IR group while IP reduced the infarct size to 27 7±1 5%(P<0 01). (3) DNA ladder pattern of ischemic myocardium was revealed by agrose gel electrophoresis in IR group while it was not found in IP group. Apoptotic cardiomyocytes were sparse within the ischemic myocardium at risk in IP as compared with those in IR heart. Apoptosis rate of the ischemic myocardium from IR and IP groups detected by flow cytometry was 11 2±0 4% and 6 35±0 2%(P<0 01), respectively. (4) Fas and Bax protein expression in the ischemic myocardium of IR and IP groups was elevated as compared with those in non ischemic myocardium group (P<0 05). The Fas protein expression of IR group was higher than that of IP group (P<0 05). Bcl 2/Bax ratio of IR group was lower than that in non ischemic myocardium (P<0 01). From the results, it is suggested that IP decreases cardiomyocytic apoptosis induced by IR and this action is mediated by the reduction of Fas protein expression.