丙酮酸对缺血/再灌注大鼠心肌的保护作用

目的:探讨丙酮酸(Pyr)对缺血/再灌注(I/R)大鼠心肌的影响及其可能的机制。方法:30只SD成年大鼠随机分为假手术(Sham)组、I/R组及I/R+Pyr组,每组10只。I/R+Pyr组大鼠于再灌前5 min,开始持续性静脉灌注Pyr 2 h25 mg/(kg·h)]。再灌注2 h后,利用多道生理记录仪检测大鼠在体血流动力学指标:平均动脉压(MABP)、左室收缩压(LVSP)及左室最大收缩、舒张末压微分(±LV dP/dt max)。采用Western blot方法检测磷酸化-JNK(p-JNK)和总的JNK(t-JNK)表达。用原位缺口末端标记法(TUNEL)评价心肌细胞的凋亡。结果:I/R组的MABP、LVSP、±LV dP/dt max显著低于Sham组(P0.01),Pyr干预可增加I/R后MABP、LVSP及±LV dP/dt max的水平(P0.05)。与Sham组相比,I/R组大鼠左心室p-JNK的水平明显增高(P0.01);而Pyr可降低大鼠左心室p-JNK的水平(P0.01),并抑制心肌细胞凋亡(P0.05)。结论:Pyr可改善I/R大鼠心肌的功能,抑制心肌细胞凋亡,其机制可能与抑制JNK信号的激活有关。

Protection of pyruvate on heart against ischemia/reperfusion injury

AIM： To investigate the effect of pyruvate on myocardial ischemia/reperfusion （I/R） injury and the underlying mechanism. METHODS ： The animal model of myocardial I/R injury was induced by 30 min of left anterior descending coronary occlusion followed by 2 h of reperfusion. Thirty rats were ran- domly divided into three groups： sham group, I/R group and I/R plus pyruvate treatment （I/R ＋ Pyr） group. Pyruvate was intravenously infused at 25 mg/（ kg·h） for 2 h, 5 min before reperfusion. Hemody- namic parameters （including LVSP, MABP and ±LV dP/dtmax,） phosphorylation and total levels of JNK were determined and cardiomyocyte apoptosis was evaluated by TUNEL staining. RESULTS： LVSP, MABP and ± LV dP/dtmax, decreased in I/R group and pyruvate treatment reversed these effects, p-JNK level increased in I/R group compared with that in sham group. Pyruvate inhibited p-JNK activation but did not change JNK expression. The index of apoptotic cardiomyocytes decreased with pyruvate treatment compared with that in I/R group. CONCLUSION： Pyruvate improves the myocardial function and inhibits myocardial apoptosis, which may result from the inhibition of JNK phosphorylation in the rat myocardial I/R model.