压力超负荷心力衰竭大鼠心室肌电生理失稳态及缝隙连接蛋白Cx43的变化

摘要

Objective To investigate the electrical instability and connexin 43 (Cx43) expression changes in left ventricles of heart failure (HF) rats induced by pressure overload. Methods Surgical abdominal aortic stenosis was used to prepare pressure overload induced heart failure model in SD rats. The rats with left ventricular end-diastolic pressure (LVEDP) ≥ 15 mmHg were categorized into HF group. Sham-operated rats served as controls. After 32 weeks, cardiac function of the rats was analyzed with carotid artery canalization and ultrosound B examination. The electrophysiological markers were also investigated. The changes in cardiac electrical instability and gap junction remodeling in left ventricles of rats were characterized by immunoblotting and transmission electron microscopy. Results HF rats presented obvious cardiac electrical instability and cardiac dysfunction. The heart rate, QT-interval, LVEDP and ventricular effective refractory period (VERP) increased significantly, and left ventricular ejection fraction decreased significantly in HF group. The expression of Cx43 in left ventricle was decreased significantly (0.929±0.095 vs 1.250±0.083, P＜0.05) in HF group. Transmission electron microscopy revealed gap junction remodelling in HF rats. Conclusion Pressure overload induced HF rats present obvious gap junction remodelling in ventricles, which may be related to electrical instability in ventricles.%目的 观察压力超负荷所致心力衰竭(HF)大鼠心室肌电生理失稳态和缝隙连接蛋白Cx43表达的变化.方法 采用腹主动脉缩窄法建立压力超负荷大鼠HF模型,取左室舒张末压≥15 mmHg的存活大鼠入HF组,另设假结扎对照组.术后32周两组大鼠以颈总动脉插管法和心脏B超测定心功能,并检测电生理指标,以免疫印迹方法检测心肌细胞Cx43蛋白表达的变化,通过透射电镜观察心室肌缝隙连接分布的变化.结果 HF大鼠出现明显电生理失稳态和心功能不全,左室舒张末压明显增高而心室有效不应期明显延长,左室射血分数明显下降,同时大鼠心室肌中缝隙连接蛋白Cx43表达明显下调(0.929±0.095 vs 1.250±0.083,P<0.05)并出现空间重构.结论 压力超负荷所致HF大鼠心室肌存在明显缝隙连接重构,这可能是导致HF时心肌电生理重构的重要机制.