摘要:
目的:研究阻断Ryanodine受体对兔心肌肥厚触发性室性心律失常发生的影响。方法:选择日本长耳兔,通过缩窄腹主动脉建立心肌肥厚模型(LVH组),并设立假手术组(仅游离腹主动脉,不进行缩窄)作为对照。8周后应用超声心动图证实心肌肥厚形成,采用酶解法分离左室心肌细胞,应用全细胞膜片钳技术记录动作电位,观察在异丙肾上腺素(1μmol/L)灌流和快频率(5Hz)电刺激条件下,单个心肌细胞晚期后除极(DAD)和触发活动的发生率,以及预先分别灌流钙调蛋白激酶Ⅱ抑制剂KN-93(1μmol/L)和Ryanodine受体阻滞剂兰尼碱(10μmol/L)对肥厚心肌细胞DAD和触发活动发生率的影响。结果:假手术组、LVH组、KN-93组和兰尼碱组DAD的发生率分别为0、85%、35%和20%,触发活动的发生率分别为0、60%、20%和10%,KN-93组和兰尼碱组DAD和触发活动的发生率较LVH组显著降低(P<0.05)。结论:阻断Ryanodine受体能够有效抑制兔心肌肥厚触发性室性心律失常的发生,Ryanodine受体有望成为防治该类心律失常的新靶点。
Abstract:
Objective:To investigate the effect of Ryanodine receptor blockage on triggered ventricular arrhythmia in rabbits with left ventricular hypertrophy(LVH).Method:Japanese rabbits were established LVH models by the coarctation of the abdominal aorta,while those in the sham group did not undergo the coarctation.After 8 weeks,single left ventricular myocyte was isolated by enzymatic dissociation method and action potential(AP) was recorded using whole cell patch clamp technique.Perfused with Tyrode's solution containing isoprenaline(1 μmol/L),the frequency of delayed afterdepolarization(DAD) and triggered activity was recorded under high-frequency stimulation stimulation(5 Hz).And the effect of KN-93 and Ryanodine perfusion on the frequency of DAD and triggered activity was observed.Result:The frequency of DAD was 0 in sham group,85% in LVH group, 35% in KN-93 group,and 20% in Ryanodine group.The frequencies of triggered activity were 0,60%,20%,and 10%,respectively.The frequencies of DAD and triggered activity in KN-93 and Ryanodine groups were much lower than those in LVH group(P<0.05).Conclusion:Blockage of Ryanodine receptor is a new method of treatment which effectively reduce the occurrence of triggered ventricular arrhythmia in rabbits with LVH.