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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

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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。

Abstract:

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.

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