三硝基丙酸预处理对缺血-再灌注兔心肌细胞凋亡的影响

目的 观察三硝基丙酸(3-NPA)预处理对缺血-再灌注兔心肌细胞凋亡的影响及其机制.方法 24只新两兰大耳兔随机分为对照组(C组)、实验组(3-NPA组)和阻滞剂组(5-HD)组),每组8只.5-HD组在开胸前24 h通过耳缘静脉注射特异性线粒体NIP敏感钾通道阻滞剂5-羟基癸酸(5 mg·kg-1),C组和3-NPA组注射同样体积的生理盐水.10 min后3-NPA组和5-HD组注射3-硝基丙酸(3mg·kg-1),C组注射同样体积的生理盐水.通过结扎兔左冠状动脉建立心肌缺血-再灌注动物模型,三组缺血 30 min再灌注120 min.检测再灌注120 min后心肌梗死面积、心肌细胞凋亡指数、Bcl-2和Bax蛋白的表达.对实验数据进行方差分析榆验.结果 3-NPA组的心肌梗死面积显著低于其它C组[(0.26±0.07)vs.(0.45±0.09),P＜0.01]和5-HD组[(0.26±0.07)vs.(0.40±0.07),P＜0.01];C组和5-HD组之间没有显著性差异[(0.45±0.09)vs.(0.40±0.07),P＞0.05].3-NPA组心肌细胞凋亡指数明显小于C组[(27.72±5.18)vs.(45.91±10.54),P＜0.01]和5-HD组[(27.72±5.18)vs.(43.44±7.33),P＜0.01].3-NPA组bcl-2表达高于另外两组[(0.123±0.046)vs.(0.079±0.019),(0.080±0.019),P＜0.05],而Bax明显低于另外两组[(0.095±0.020)vs.(0.14±0.05) and(0.15±0.05),P＜0.05].结论 3-NPA预处理对缺血-再灌注心肌具有良好的扰凋亡作用,这与其开放断线粒体ATP敏感钾通道有关.

Preconditioning with 3-nitropropionic acid reduces myocardial apoptosis induced by ischemia-reperfusion injury

Objective To investigate the effects of preconditioning with 3-nitropropionie acid on myocardial apoptosis induced by ischemia-reperfusion injury.Method Twenty-four rabbits were randomly divided into control group(group C,n=8),precondition group(group 3-NPA,n=8)and 5-HD group(group 5-HD,n=8).The group 5-HD was treated intravenously with 5 mg·kg-1 5-HD(ATP-sensitive potassium channels blocker),group C and group 3-NPA received normal saline instead of 5-HD.Ten minutes later,5-HD group and 3-NPA group were injected with 3-NPA(3 mg·kg-1)and the group C was injected with normal saline.Twenty-four hours later,the left anterior descending coronary artery was ligated for 30 min and then unclamped for 120 min to estabhsh ischemi-a-reperfitsion injury model.After reperfusion,the infarct sizes of ventricular myocardium,apoptotic myocardial cells and the expressions of Bcl-2 and Bax protein were measured.Results Infarct sizes and apoptotic myocardial cells in group 3-NPA were less than those in the others(P＜0.01).The expressions of Bcl-2 in group 3-NPA.in-creased as compared with group C(P＜0.05)and group 5-HD(P＜0.05),whereas the expressions of Bax in group 3-NPA decreased as compared with group C(P＜0.05)and group 5-HD(P＜0.05).Conclusions Preconditioning with 3-nitmpropionie acid reduces myocardial apoptosis induced by isehemia-reporfusion injury which is attributed to the opening of mitochondrial KATP channels.