肝素和N-乙酰基肝素对缺血再灌注心肌的保护作用及其机制

Cardioprotective effects of heparin and N-acetylheparin on myocardium undergoing ischemia-reperfusion and their mechanism

目的 探讨肝素对心肌的保护作用机理 ,为肝素在冠心病临床上的合理应用提供参考。方法 将 48只雄性SD大鼠随机分为生理盐水 (NS)组、N -乙酰基肝素 (N Hep)组和肝素 (Hep)组。大鼠经颈静脉给药后 2h ,复制心肌缺血再灌注模型。氯化三苯基四氮唑 (TTC)染色法评价心肌梗死范围 ;放射免疫法检测血清肿瘤坏死因子α(TNFα) ,以硫代巴比妥酸法测定血清丙二醛 (MDA)含量。结果 (1)Hep组和N -Hep组心肌梗死范围均显著低于生理盐水组 (P <0 .0 1)。(2 )用药前 ,活化部分凝血活酶时间 (aPTT)在组间差异无显著性意义(P >0 .0 5 ) ;在用药后 30min和 12 0min ,Hep组aPTT比NS组和N Hep组显著延长 (P<0 .0 0 1)。(3)Hep和N Hep组血清MDA和TNFα水平均显著低于NS组 ,而Hep组与N Hep组比较差异无显著性意义。结论 肝素的心肌保护作用可能并不依赖于其抗凝活性 ;

Objective To determine the mechanism of protective effects of heparin on myocardicem,so as to provide reference for reasonable use of heparin in coronary heart disease.Methods Forty-eight male SD rats were randomly divided into three groups(n=16 for each group):normal saline group(NS),N-acetylheparin group(N-Hep) and heparin group(Hep).Two hours after venous administration of above drugs,rat model of myocardial ischemia-reperfusion was reproduced.Myocardial infarction size was determined by TTC stain.Tumor necrosis factor-α(TNFα) and malondialdehyde (MDA)in serum were respectively measured by radioimmunoassay (RIA) and thiobarbituric acid assay.Results (1) Myocardial infarction size in both Hep group and N-Hep group was lower significantly than that in NS group (P< 0.001); (2) There was no difference in activated partial thromboplastin time(aPTT) among three groups before administration of drugs,but 30 min and 120 min after drug administration,aPTT in Hep group was longer significantly than that in both NS group and N-Hep group (P<0.001);(3) Serum levels of MDA and TNFα in Hep group and N-Hep group were higher significantly than those in NS group,but there was no significant difference between Hep group and N-Hep group.Conclusions Cardioprotective effect of heparin may not depend on its anticoagulation property. Cardioprotective effects of heparin and N-acetylheparin may be related to their inhibition of TNFα expression in myocardium and reduction of free radical injury of myocardium.