CaMK Ⅱ-ryanodine受体信号途径在心肌肥厚兔触发性室性心律失常中的作用  

Roles of CaMK Ⅱ-ryanodine receptor signal transduction pathways in triggered ventricular arrhythmia of rabbits with myocardial hypertrophy

作　　者：柯俊[1] 肖幸[2] 陈锋[1] 贺莉[3] 戴木森[1] 王晓萍[1] 陈兵[1] 陈敏[1] 张存秦[2] 

机构地区：[1]福建医科大学省立临床医学院福建省立医院急诊内科,福州350001 [2]华中科技大学同济医学院附属同济医院综合科 [3]华中科技大学同济医学院心内科

出　　处：《中华急诊医学杂志》2012年第4期392-396,共5页Chinese Journal of Emergency Medicine

基　　金：福建省自然科学基金面上项目（2008J0075）;福建省科技重点项目（2010y0011）

摘　　要：目的研究CaMKⅡ-ryanodine受体信号途径在心肌肥厚兔触发性室性心律失常中的作用。方法将40只新西兰大白兔随机（随机数字法）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＋兰尼碱组（兰尼碱组），每组10只。LVH组、KN-93组及兰尼碱组通过缩窄腹主动脉制备兔心肌肥厚模型，Sham组仅游离腹主动脉不进行缩窄。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，KN-93组和兰尼碱组首先给予各自药物预灌，然后观察在异丙肾上腺素（1μxmol／L）灌注和快频率程序刺激条件下各组触发活动和室性心动过速的发生率。结果Sham组、LVH组、KN-93组（1μmol／L）和兰尼碱组（10μmol／L）触发活动的发生率分别为0／10、10／10、4／10和1／10，室性心动过速的发生率分别为0／10、9／10、3／10和1／10，多形性室速或室颤的发生率分别为0／10、7／10、2／10、1／10，KN-93组和兰尼碱组触发活动和室性心动过速的发生率较LVH组明显降低（P〈0．05）。结论KN-93和兰尼碱能够有效抑制心肌肥厚兔触发性室性心律失常的发生，CaMKⅡ—ryanodine受体信号途径可成为抗心律失常治疗的全新靶点。Objective To determine the effect of calmodulin-dependent kinase Ⅱ （CaMK Ⅱ ） - ryanodinereceptor pathway signaling in rabbits with left ventrieular hypertrophy （LVH） and triggered ventricular arrhythmia. Methods Forty New Zealand rabbits were randomized into four groups （ n = 10 per group） ： the sham operation group, LVH group, KN-93 （CaMK Ⅱ inhibitor） group （LVH ＋ KN-93）, and the ryanodinegroup （ LVH ＋ ryanodine）. Rabbits in the LVH, KN-93, and ryanodinegroups were used to establish a left ventrieular hypertrophy model by the eoarctation of the abdominal aorta, while the rabbits in the sham operation group did not have the coarctation. After eight weeks, action potentials （APs） were recorded simultaneously in the endoeardium and epicardium, and transmural electrocardiogram （ECG） was also recorded in the wedge shaped models of rabbits＇ left ventricular myocardium. Drugs were administered to animals in the KN-93 and ryanodinegroups respectively, and the frequency of triggered APs and ventricular tachyeardia were recorded after isoprenaline （ 1μmol/L） , and high-frequency electrical stimulation were given to rabbits. Results The incidences （animals/group） of triggered APs were： sham, 0/10; LVH, 10/ 10; KN-93, 4/10; and ryanodine, 1/10. The incidences of ventricular taehycardia induced were 0/10, 9/ 10, 3/10, and 1/10, respectively. The incidences of triggered ventricular arrhythmias in the KN-93 group and ryanodine groups taehyeardia or ventrieular fibrillation were 0/10, 7/10, 2/10, and 1/10, respectively. The incidences of triggered ventricular arrhythmias in the KN-93 group and ryanodine groups were much lower than that in the LVH group （P 〈 0. 05）. Conclusions KN-93 and ryanodinecan effectively reduce the occurrence of triggered ventricular arrhythmia in rabbits with LVH. The CaMK Ⅱ-ryanodine signaling pathway can be used as a novel target site of treating ventricular arrhythmia.

关 键 词：钙调蛋白激酶Ⅱ RYANODINE受体 信号转导途径 触发活动 动作电位 跨壁心电 图 室性心律失常 心肌肥厚 

分 类 号：R541.7[医药卫生—心血管疾病]