卡维地洛与美托洛尔在犬急性心肌梗死晚期再灌注中的心肌保护作用的比较

目的探讨卡维地洛在犬急性心肌梗死(AM I)晚期再灌注中的心肌保护作用及其与美托洛尔的比较。方法18条健康成年杂种犬随机平均分为3组:单纯晚期再灌注组(late reperfusion group,LR)、晚期再灌注预加美托洛尔组(late reperfusion+m etoprolol group,LR+M)、晚期再灌注预加卡维地洛组(late reperfusion+carved ilol group,LR+C)。分别灌服生理盐水、美托洛尔(1 mg.kg-1.d-1)、卡维地洛(1 mg.kg-1.d-1)共7 d。所有犬于d 7灌药2 h后开胸结扎左冠状动脉前降支(距离起点5 mm)6 h,再灌注6 h,制成AM I晚期再灌注模型。后处死取左室心肌梗死边缘区,比色法测定心肌超氧生物歧化酶(SOD)和还原性谷胱甘肽酶(GR)活性、丙二醛(MDA)含量,免疫组化法检测心肌Fas和FasL蛋白表达,TUNEL法测心肌细胞凋亡指数(AI)。结果与LR相比,LR+M的SOD、GR活性以及MDA含量无改变(P>0.05),而LR+C的SOD、GR活性均升高(P<0.01),MDA含量降低(P<0.05);进一步研究发现与LR相比,梗死边缘区心肌Fas和FasL蛋白表达以及细胞AI在LR+M明显下降,差异有显著性(P<0.05),并且LR+C比LR+M亦下降明显,两组相比差异有显著性(P<0.05)。结论卡维地洛和美托洛尔对急性心肌梗死晚期再灌注造成的损伤都有保护作用,但卡维地洛的保护作用优于美托洛尔,可能与其抗氧化作用有关。

Comparison between cardioprotection of carvedilol and metoprolol on late reperfusion of acute myocardial infarction in canine

Aim To compare cardioprotection effects between carvedilol and metoprolol in canine late reperfusion of acute myocardial infarction.Methods Eighteen anesthetized dogs were randomly divided into three groups: late reperfusion group(LR,n=6),late reperfusion after metoprolol treatment group(LR+M,n=6),and late reperfusion after carvedilol treatment group(LR+C,n=6),respectively orally giving physiological saline,metoprolol(1 mg·kg~(-1)·d~(-1)),and carvedilol(1 mg·kg~(-1)·d~(-1)) for seven days,and then late reperfusion of acute myocardial infarction model was made by ligating the coronary for 6 h,followed by reperfusion for 6 h.SOD,GR activity and MDA content of infarction brim myocardium were detected by colorimetry,Fas/FasL were detected by immunohistochemistry,apoptosis index(AI) were detected by TUNEL.Results Compared with LR,Myocardial MDA content in LR+C was decreased,and SOD and GR activities were significantly higher,but LR+M did not change.The expression of Fas/FasL and apoptosis index were significantly lowered in LR+M and LR+C,especially in LR+C.Conclusion Carvedilol and metoprolol have cardioprotection on late reperfusion of acute myocardial infarction,and carvedilol is superior to metoprolol and the pharmacological effects may due to its antioxidant effect.