缝隙连接在长QT综合征2型电活动不稳定中的作用  

The role of gap junction in electrophysiological instability in rabbit wedge ventricular model of LQT2

作　　者：倪明科[1] 张存泰[1] 李连东[1] 阮磊[1] 王琳[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院心内科,湖北武汉430030

出　　处：《中国心脏起搏与心电生理杂志》2010年第3期243-246,共4页Chinese Journal of Cardiac Pacing and Electrophysiology

基　　金：国家自然科学基金资助课题(项目编号:30370573)

摘　　要：目的探讨缝隙连接(GJ)的功能改变在长QT综合征2型(LQT2)模型中电活动不稳定中的作用。方法纽西兰大白兔30只,随机分为正常对照组、LQT2组和抗心律失常肽(AAP10)组。应用0.5μmol/L的E-4031对兔左室楔形心肌组织块进行灌流制备LQT2模型。采用浮置玻璃微电极法同步记录心内膜、心外膜心肌细胞跨膜动作电位及跨室壁心电图。观察各组QT间期和跨室壁复极离散度(TDR)的变化,通过免疫印迹和免疫荧光的方法观察GJ的分布和磷酸化状态的改变。结果①LQT2组QT间期较正常对照组显著延长(P<0.05),TDR较正常对照组显著增大(P<0.05)以及缝隙连接去磷酸化水平较正常对照组显著增高(P<0.01);②AAP10组QT间期较LQT2组显著缩短(P<0.05),TDR较LQT2组显著减小(P<0.05或0.01)以及缝隙连接去磷酸化水平较LQT2组显著降低(P<0.05或0.01);③三组的Cx43总量无明显差异(P>0.05)。结论 GJ的功能改变是LQT2模型中电活动不稳定的重要因素。Objective To test the hypothesis that the functional change of gap junction contributes the electrophysiologieal instability in rabbit wedge ventrieular model of LQT2. Methods Thirty female New Zealand white rabbits weighing 1.8 -2.2 kg were randomly assigned to normal control group, LQT2 model group and AAP10 group. An arterially-perfused rabbit left ventricular wedge preparation and an Ikr blocker, E-4031, was used to establish a model of LQT2. Transmural ECG as well as action potential from both endoeardium and epicardium were simultaneously recorded in the whole process of all experiments. Changes of Cx43 and dephosphorylated Cx43 were measured by Western blot, the distribution of Cx43 and dephosphorylated Cx43 were examined by confocal laser scanning microscopy. Results （1）In LQT2 model, the QT interval prolonged（P 〈 0.05 ） , TDR decreased （P 〈 0.05 or 0.01 ） and dephosphorylated Cx43 contents in LQT2 group increased significantly comparing to the normal control group （ P 〈 0.01 ） ; （2）the QT interval shortened（ P 〈 0.05 ）, TDR decreased （P 〈 0.05 or 0.01 ） and depbosphorylated Cx43 contents decreased significantly in AAP10 group comparing to the LQT2 group （P 〈 0.01 ）. （3）No significant change of total Cx43 contents was observed among normal control group, LQT2 group and AAP10 Group（ P 〉 0.05 ）. Conclusion This study provides a direct evidence that the functional change of gap junction contributes the eleetrophysiological instability in rabbit ventricular model of LQT2.

关 键 词：电生理学 缝隙连接 长QT综合征 跨室壁离散度 抗心律失常肽 缝隙连接蛋白 左室楔型心肌组织块 

分 类 号：R331.38[医药卫生—人体生理学] R541.7[医药卫生—基础医学]