卡维地洛和美托洛尔对缺血再灌注损伤心肌细胞凋亡的影响

目的研究卡维地洛和美托洛尔对动脉粥样硬化家兔缺血再灌注损伤心肌细胞凋亡和脂质过氧化的影响。方法48只家兔随机分为4组（各组12只）：假手术组、模型组、美托洛尔组、卡维地洛组。采用高脂饮食并免疫损伤制作动脉粥样硬化模型，4周后给予药物，实验第8周时建立家兔心肌缺血再灌注模型。心电监护计数心率，测定家兔血脂指标（CH、TG）、超氧化物歧化酶（SOD）和丙二醛（MDA），采用免疫组化的方法检测核因子-KBP65（NF-KBp65）及Fas蛋白的表达，采用末端标记原位细胞凋亡法检测心肌凋亡细胞。结果药物干预组心率较不用药组心率减慢（P〈O．01）。血清SOD水平模型组较假手术组明显降低（P〈O．01），美托洛尔组和卡维地洛组血清SOD水平较模型组明显升高（P〈0．01）；卡维地洛组较美托洛尔组明显升高（P〈O．01）。模型组血清MDA水平、心肌细胞NF-闎、Fas蛋白表达和凋亡指数较假手术组明显升高（P〈0．01），美托洛尔组和卡维地洛组各指标较模型组明显降低（P〈0．01），卡维地洛组各指标较美托洛尔组明显降低（P〈0．01）。结论美托洛尔和卡维地洛均对缺血再灌注心肌细胞有保护作用，可能与它们抗氧化减轻脂质过氧化损伤，从而减少Fas和NF-kB蛋白的表达抗凋亡有关；卡维地洛对减少缺血再灌注心肌细胞凋亡方面优于美托洛尔。

Effect of Carvedilol and Metoprolol on ischemical reperfusion injury about myocardial apoptosis in rabbits

Objective To study the effect of carvedilol and Metoprolol on ischemical reperfusion injury in rabbits which were fed with high fat diet by testing their impact on the apoptosis of myocardial cell and relieving oxidative damage. Methods 48 rabbits were randomly divided into 4 groups： sham operation group, operation group, Metoprolol group and Carvedilol.All the rabbits were fed with high fat diet and immunologic injury by injecting bovine serum albumin. After tour weeks the rabbits in Metoprolol group and Carvedilol group were given the drug. After the second tour weeks,counted the heart rate and carried out the ischemical reperfusion injury operation. Blood biochemical tests （TG CH SOD MDA） were done to evaluate the influence of Carvedilol and Metoprolol. The expression of NF-k Bp65 and Fas were measured by the method of immunohistochemistry. The enumeration of the apoptosis ceils was detcted by means of TUNEL. Results The heart rate in Metoprolol group and Carvedilol group was lower than that of sham operation group and operation group （P 〈0.01）. The level of serum SOD was lower than that of sham group（P 〈0.01）. In Metoprolol group and Carvedilol group ,the level of serum SOD had statistical difference than that of model group（P 〈0.01 ）, there was statistical differenoe between the Metoprolot group and Carvedilol group（P 〈0.01）.The expression of NF-~Bp65 and Fas and the enumeration of the apoptosis cells and the level of serum MDA in operation group was higher than those of sham operation group（P 〈0.01）,but in Metoprolol group and Carvedilol group they decreased（P 〈0.01）. There was statistical differences between Metoprolol and Carvedilol group （P 〈0.01）. Conclusions Metoprolol and Carvedilol can protect the myocardium from ischemical reperfusion injury. This was possiblely because their relieving oxidative damage induces anti-apoptosis effect by inhibiting the exepression of NF-~ B and Fas. Carvedilol group have a better protective effect on ischemical reperfusion injury than Metoprolol group.