替格瑞洛对大鼠心肌梗死再灌注后心律失常及钙离子通道影响

Influence of ticagrelor on arrhythmia and calcium channel in rats after myocardial infarction reperfusion injury

目的研究替格瑞洛对心肌梗死再灌注动物模型心律失常及心室肌细胞L型钙离子通道的影响。方法选择24只健康的SD雄性大鼠,随机分为3组(均为8例):假手术组(sham组,只穿线不结扎血管)、缺血再灌注模型组(I/R组,缺血30 min后再灌注120 min)、替格瑞洛组(ticagrelor组,术前2 h给SD大鼠灌胃替格瑞洛20 mg/kg)。监测Ⅱ导联心电图,观察各实验组再灌注后发生室性早搏、室速、室颤的情况;全细胞膜片钳记录各实验组心室肌细胞L型钙电流的变化情况。结果与I/R组比较,ticagrelor组室性早搏个数明显减少,室速及室颤发生率明显降低(P<0.05)。Sham组、I/R组、ticagrelor组L型钙峰值电流密度的比较中,I/R组较sham组明显增高[(-9.4±0.6)pA/pF vs.(-4.3±0.5)pA/pF,P<0.05],ticagrelor组较I/R组明显降低[(-7.1±1.0)pA/pF vs.(-9.4±0.6)pA/pF,P<0.05]。与I/R组相比,ticagrelor组可明显加快L型钙通道的失活过程(P<0.05),不影响L型钙通道的激活过程(P>0.05)。结论替格瑞洛能够通过显著降低L型钙电流,从而减少心肌缺血动物模型再灌注心律失常的发生。

Objective To study the influence of ticagrelor on arrhythmia and L-type calcium channel in ventricular myocytes in animal model of myocardial infarction reperfusion injury.Methods Male and healthy SD rats(n=24)were divided randomly into 3 groups(each n=8):sham-operation group(without ligation),ischemia reperfusion model group(I/R group,ischemia for 30 min and reperfusion for 120 min)and ticagrelor group(20 mg/kg of ticagrelor orally 2 h before ligation).Lead-II of electrocardiograph was monitored,and the incidence of arrhythmias including ventricular premature beat(VPB),ventricular tachycardia and ventricular fibrillation(VF)were observed in 3 groups after reperfusion.The changes of L-type calcium channel current in ventricular myocytes were recorded by using whole cell patch clamp in all groups.Results Compared with I/R group,the number of VPB decreased significantly,and incidence rate of ventricular tachycardia and VF decreased significantly in ticagrelor group(P<0.05).The comparison in peak current densities of L-type calcium channel in 3 groups showed that it increased significantly in I/R group than that in sham-operation group[(-9.4±0.6)pA/pF vs.(-4.3±0.5)pA/pF,P<0.05],and decreased significantly in ticagrelor group than that in I/R group[(-7.1±1.0)pA/pF vs.(-9.4±0.6)pA/pF,P<0.05].Compared with I/R group,the inactivation process of L-type calcium channel was significantly accelerated(P<0.05)and activation process was not affected(P>0.05)in ticagrelor group.Conclusion Ticagrelor can reduce the incidence rate of arrhythmia through decreasing significantly L-type calcium channel current in animal model with myocardial ischemia after reperfusion injury.