卡维地洛和庚醇对心肌缺血再灌注损伤的保护作用

Protective effects of carvedilol and heptanol against myocardial ischemia reperfusion injury

目的研究卡维地洛(CVD)、庚醇(HT)在缺血再灌注心肌损伤中作用。方法通过建立的心脏缺血再灌注模型,采用2%氯化三苯四唑(TTC)染色测量心肌梗死的重量,监测心肌型肌酸激酶同功酶(CK-MB)、乳酸脱氢酶(LDH)、丙二醛(MDA)和一氧化氮(NO)等的变化。观察CVD、HT对心肌梗死的影响。结果在缺血30min,再灌注6h后,CVD减少CK-MB、LDH及MDA的释放,稳定NO的分泌。HT组在一定程度上也减少了LDH、CK-MB的释放,但对NO、MDA的释放似乎没有太大影响。CVD组的大鼠梗死心肌仅占左心室心肌重量的(6.2±1.1)%,比对照组减少了51.6%。HT组梗死心肌占左心室心肌重量的(7.4±1.0)%,比对照组减少了42.2%。HE常规染色发现CVD组心肌细胞损伤程度明显减轻,粒细胞浸润也明显减少,大部分仅表现肌纤维肿胀和断裂。CVD可以防止内皮型一氧化氮合酶的减少。电镜下,CVD组和HT组心肌润盘肌丝、线粒体等损伤较轻。结论CVD通过β受体拮抗、抗氧化等方面的作用来保护心肌。HT可能是使缝隙连接可逆性解藕联产生心肌保护作用。

Objective To evaluate the effects of cardioprotection provided by carvedilol （CVD） and heptanol （HT） in a rat model of acute myocardial ischemic-reperfusion injury. Methods Myocardial infarction was induced by left descending anterior coronary artery ligation for 30min,followed by 6h of reperfusion in rats. At the end of the reperfusion period, the infarct size was determined by 2% TTC staining. LDH,CK-MB,NO, MDA in blood and tissue samples of infarcted areas were measured. Results In CVD-treated rats, there was decrease in LDH,CK-MB and MDA, but no significant change in NO（P〉0.05）. HT also could decrease LDH and CK-MB,but had no influence on NO and MDA. The myocardial infarct size was（6.2±1.1）% of the left ventricle in CVD group,and （12.8±1.2）% in vehicle-treated rats. CVD produced 51.6% reduction in infarct size（P〈0.01）. HT reduced infarct size by 42.2%（P〈0.01）. In control group, HE-stained wax section examination and thin-section electron microscopic examination showed conspicuous extensive and focal necrosis of myocytes, disorganized intercalated disks and a large number of neutrophil infiltration in ischemic areas. In CVD group, the damage degree of myocytes and intercalated disks and neutrophil infiltration were markedly reduced. CVD could prevent the decrease in endothetial nitric oxide synthase. Conclusion CVD and HT provide powerful cardioprotective effect on ischemic-reperfused myocardium. CVD has antioxidative effect, reduces myocardial oxygen demand and neuotrophil infiltration in ischemic area, thus protecting myocardium. HT provides cardioprotection by reversible inhibition of gap junctional intercellular communication and intracellular Ca^2＋ fluctuation.