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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-κBp65(NF-κBp65)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<0.01)。血清SOD水平模型组较假手术组明显降低(P<0.01),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<0.01)。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-κB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。
Objective To investigate the effects of carvedilol and metoprolol on myocardial cell apoptosis and lipid peroxidation in rabbits with atherosclerotic ischemia-reperfusion injury. Methods 48 rabbits were randomly divided into 4 groups (12 in each group): sham operation group, model group, metoprolol group and carvedilol group. The model of atherosclerosis was made by high-fat diet and immunostaining. After 4 weeks, the drug was given. At the 8th week, the model of myocardial ischemia-reperfusion in rabbits was established. Cardiac electrocardiogram (ECG) was used to count the heart rate. Serum lipids (CH, TG), superoxide dismutase (SOD) and malondialdehyde (MDA) were measured and the expression of nuclear factor-κBp65 The expression of Fas protein was detected by end-labeled in situ apoptosis assay. Results The heart rate of drug-treated group was lower than that of non-drug-treated group (P <0.01). Serum SOD levels in model group were significantly lower than those in sham-operated group (P <0.01). Serum SOD level in metoprolol group and carvedilol group was significantly higher than that in model group (P <0.01) The group of Tolol was significantly higher (P <0.01). The levels of serum MDA, NF-|ÊB, Fas protein and apoptosis index in model group were significantly higher than those in sham operation group (P <0.01). The indexes in metoprolol group and carvedilol group were significantly lower than those in model group (P <0.01). The carvedilol group was significantly lower than the metoprolol group (P <0.01). Conclusion Both metoprolol and carvedilol have a protective effect on myocardial cells during ischemia-reperfusion, which may be related to their anti-oxidant effects on lipid peroxidation injury and anti-apoptotic effect of Fas and NF-κB protein. Vedlotol is superior to metoprolol in reducing ischemia-reperfusion cardiomyocyte apoptosis.