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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。
Objective: To investigate the effect of blockade of Ryanodine receptor on cardiac hypertrophy-induced ventricular arrhythmia in rabbits. Methods: The Japanese long-eared rabbits were selected and the model of cardiac hypertrophy was established by narrowing the abdominal aorta (LVH group). The sham operation group (free abdominal aorta only, without constriction) was established as a control. Eight weeks later, cardiac hypertrophy was confirmed by echocardiography. Left ventricular myocardial cells were isolated by enzymatic method. Whole-cell patch-clamp technique was used to record the action potentials. Isoproterenol (1μmol / L) perfusion and fast frequency (DAD) and triggering activity of single cardiomyocytes, as well as pre-perfusion of calcineurin II inhibitor KN-93 (1μmol / L) and Ryanodine receptor blocker ryanodine (10μmol / L) on the incidence of DAD and triggering activity in hypertrophic cardiomyocytes. Results: The incidence of DAD in sham operation group, LVH group, KN-93 group and ranitidine group were 0, 85%, 35% and 20%, respectively. The incidence of triggering activity was 0,60%, 20% and The incidence of DAD and triggering activity in KN-93 and ranitidine groups was significantly lower than that in LVH group (P <0.05). Conclusion: Blocking Ryanodine receptor can effectively inhibit the occurrence of ventricular hypertrophy-induced ventricular arrhythmias. Ryanodine receptor is expected to become a new target of prevention and treatment of arrhythmia.