【摘要】 目的探讨钙调蛋白激酶Ⅱ特异性抑制剂KN-93抗肥厚心肌室性心律失常发生的机制。方法雌性新西兰大白兔随机分为4组:假手术组(sham组)、心肌肥厚组(LVH组)、心肌肥厚+KN-93组(KN-93组)、心肌肥厚+KN-92组(KN-92组),每组14只。LVH组、KN-93组及KN-92组通过缩窄腹主动脉制备兔心肌肥厚模型。8周后,制备兔左室楔形心肌块的灌注模型,同步记录心内、外膜动作电位及跨壁心电图,观察低钾(2 mmol/L)、低镁(0.25 mmol/L)蒂罗德液灌流及慢频率(2 000~4 000 ms)刺激条件下各组早期后除极(EAD)和尖端扭转型室性心动过速(Tdp)的发生率。采用胶原酶消化法分离单个心肌细胞,应用膜片钳技术记录动作电位(AP),观察低钾、低镁蒂罗德液灌流及慢频率(0.25~0.5 Hz)刺激条件下,各组EAD的发生率。结果在低钾、低镁蒂罗德液灌流及慢频率刺激条件下,兔左室楔形心肌块水平,sham组、LVH组、KN-92组(0.5μmol/L)及KN-93组(0.5μmol/L)EAD的发生率分别为0/10、10/10、9/10和5/10,Tdp的发生率分别为0/10、5/10、4/10和1/10。单个心肌细胞水平,Sham组、LVH组、KN-92组(0.5μmol/L)及KN-93组(0.5μmol/L)EAD的发生率分别为0/12、11/12、10/12和5/12。结论钙调蛋白激酶Ⅱ介导心肌肥厚兔室性心律失常的发生,其主要作用机制是通过增加EAD的发生率,从而触发室性心律失常的发生。更多还原

【Abstract】 Objective To investigate the role of calmodulin kinase Ⅱ on ventricular arrhythmias in rabbits with cardiac hypertrophy by use KN-93,a kind of calmodulin kinase Ⅱ inhibitor.Methods Fifty-six female New Zealand white rabbits were randomly divided into 4 groups:sham group,LVH group,KN-92 group and KN-93 group.In LVH group,KN-92 group and KN-93 group,the abdominal aorta was partially constricted.Eight weeks later:①The arterially perfused left ventricular wedge preparations were made,transmembrane action potentials(TAP) from epicardium and endocardium were simultaneously recorded together with a transmural ECG.The incidence of EAD and Tdp with slow stimulation(2 000-4 000 ms) and hypokalemic(2 mmol/L),hypomagnesaemic(0.25 mmol/L) Tyrode’s solution in left ventricular wedge preparations was observed;②Myocytes were isolated by enzymatic method,and whole cell patch clamp technique was used to record the action potential.The incidence of EAD with slow stimulation(0.25-0.5 Hz) and hypokalemic(2.0 mmol/L),hypomagnesaemic(0.25 mmol/L) Tyrode’s solution in single ventricular cells was observed.Results ①With slow stimulation and hypokalemic,hypomagnesaemic Tyrode’s solution in left ventricular wedge preparations,the incidence of EAD in sham group,LVH group,KN-92 group(0.5 μmol/L) and KN-93 group(0.5 μmol/L) was 0/10,10/10,9/10 and 5/10 respectively;The incidence of Tdp in sham group,LVH group,KN-92 group(0.5 μmol/L) and KN-93 group(0.5 μmol/L) was 0/10, 5/10,4/10 and 1/10 respectively;②With slow stimulation and hypokalemic,hypomagnesaemic Tyrode’s solution in single ventricular cells,the incidence of EAD in sham group,LVH group,KN-92 group(0.5 μmol/L) and KN-93 group(0.5 μmol/L) was 0/12,11/12,10/12 and 5/12 respectively.Conclusion Calmodulin kinase Ⅱ mediates the occurrence of ventricular arrhythmias in rabbits with cardiac hypertrophy by increasing the incidence of EAD.更多还原