不同剂量美托洛尔对家兔缺血再灌注损伤心肌细胞凋亡的影响

目的探讨不同剂量美托洛尔对家兔缺血再灌注损伤心肌细胞凋亡的影响。方法48只家兔随机分为4组．假手术组、模型组、小剂量美托洛尔组、大剂量美托洛尔组。采用高脂饮食并免疫损伤制作动脉粥样硬化模型。用药4周后结扎家兔左冠状动脉前降支（LAD），建立家兔缺血再灌注动物模型。测定家兔血脂指标（TG、TC）及心率，取左心室病理，应用11℃染色的方法检测各组心肌梗死面积，采用免疫组化染色半定量检测心肌核因子KBp65（NF—KBp65）及Fas蛋白的表达量．采用TUNEL法计数心肌凋亡指数：结果药物干预组心率较不用药组心率减慢（P〈0．01），大剂量美托洛尔组比小剂量美托洛尔组心率减慢（P〈0．05）；手术组的凋亡指数、Fas和NF—κB蛋白表达较假手术组明显增加（P〈0．01），大小剂量美托洛尔组凋亡指数、Fas和NF—κB蛋白的表达较模型组明显减少（P〈O．01），大剂量美托洛尔组凋亡指数、Fas和NF—κB蛋白的表达较小剂量美托洛尔组明显减少（P〈0．05）；大小剂量美托洛尔组心肌梗死面积较模型组明显减小（P〈0．01），大剂量美托洛尔组较小剂量美托洛尔组心梗面积明显减少（P〈0．01）。结论美托洛尔对缺血再灌注心肌有保护作用，减少心梗面积，可能与它减慢心率、减少心肌细胞Fas和NF—κB蛋白的表达抗凋亡有关，美托洛尔对缺血再灌注损伤心肌的保护作用呈剂量依赖性。

Effect of different dose of Metoprolol on the apoptosis of myocardial cell with ischemical reperfusion injury in atherosclerosis rabbits

Objective To investigate the effect of different dose metoprolol on the apoptosis of myocardial cell after ischemical reperfusion model in atherosclerotic rabbits. Methods Set up atherosclerotic model in 48 rabbits, randomly divided into 4 groups, sham operation group 12, model group 12, low dose metoprolol group 12 and large dose metoprolol group 12. All the rabbits were fed with high fat diet and immunologic injury. After 4 weeks, the rabbits in low dose metoprololgroup, large dose metoprololgroup were given the drug; after the second 4 weeks, carried out the ischemical reperfusion operation. Heart rate and blood biochemical tests （TG CH） and the aera of myocardial infarction and immunohistochemical analysis were done to evaluate the influence on the apoptosis of myocardial cell in ischemical reperfusion model and the inhibition effect of metoprolol. Results The heart rate in low dose metoprolol group and large dose metoprolol group was lower than that of sham operation group and the model group （P〈0.01）. In low dose metoprolol group, the heart rate was higher than that of large dose metoprolol group （P〈0.05）,In model group, the area of of myocardial infarction was higher than that of low and large dose metoprolol group （P〈0.01）,but in low dose group, the area of myocardial infarction was higher than that of large dose metoprolol group（P〈0.01 ）. The expression of NF-KBp65 and Fas and the enumeration of the apoptosis cells in operation group was higher than those of sham operation group （P〈0.01）,but in the low dose metoprolol group and large dose metoprolol group they decreased （P〈0.05）. Conclusion Metoprolol could protect the myocardium from ischemical reperfusion injury, because their anti-apoptosis effect by inhibiting the expression of NF-κB and Fas and the decrease in the heart rate.Metoprolol shows dose dependent protective effect.