不同交感-儿茶酚胺系统激活模式在心脏重塑中的作用  

Roles of Different Patterns of Sympathetic Neural Activation during Cardiac Remodeling

作　　者：徐明[1] 宋峣[1] 冯新恒[1] 郝天袍[2] 吕志珍[2] 白燕[1] 张幼怡[2] 

机构地区：[1]北京大学第三医院血管医学研究所分子心血管教育部重点实验室,北京市海淀区花园北路49号100083 [2]北大学第三医院血管医学研究所分子心血管教育部重点实验室,北京市海淀区花园北路49号100083

出　　处：《中国分子心脏病学杂志》2007年第1期21-26,共6页Molecular Cardiology of China

基　　金：国家自然科学基金(30470691和30672466);国家重点基础研究发展规划项目计划(973计划;2006CB503806)

摘　　要：目的交感神经的过度激活是导致心肌肥厚的重要因素,但它在生理性及病理性心肌重塑中所起的作用是否存在差异及其机制,目前尚不清楚。本研究旨在探讨不同的交感-儿茶酚胺系统激活模式在生理性和病理性心肌重塑中的作用及其可能的机制。方法分别采用大鼠游泳训练与去甲肾上腺素(norepinephrine,NE)微泵灌注模拟两种不同的儿茶酚胺分泌模式(间断型及持续型) ,制备心肌肥厚动物模型;利用超声心动图检测、免疫组化等手段观察心脏的功能及结构变化;采用Western blot及生化方法检测能量代谢的关键激酶——腺苷酸-活化蛋白激酶(AMP-activated protein kinase,AMPK)α亚单位的活性。结果与对照组相比,游泳训练与NE灌注均可显著增加大鼠血浆中去甲肾上腺素的水平。但是,NE灌注组大鼠的心肌肥厚和组织纤维化程度均较游泳训练组明显增强,且伴有心功能的进行性下降,出现心力衰竭。NE灌注同时可诱导心肌组织AMPK活性显著增强。结论上述资料提示,不同的交感-儿茶酚胺激活模式可能是影响心肌重塑转归的一个重要因素,而AMPK可能参与调控病理性心脏重塑过程中能量代谢的适应性变化。Objective The excessive activation of sympathetic nerve system plays an essential role in cardiac hypertrophy. It still remains unclear whether this activation confers different effects and mechanisms between the physiological and pathological cardiac hypertrophy. The present study aims at exploring the effects of different patterns of catecholamine release on the physiological and pathological cardiac remodeling and the underlying mechanism. Methods Two models based on different patterns of catecholamine secretion, intermittent and continuous secretion, were established by using forced swimming training or norepinephrine （NE） infusion with osmotic pumps in rats respectively. The alteration in cardiac structure and function were determined through echocardiography and immunohistochemistry. The α subunit and its phosphorylation level of AMP-activated protein kinase （ AMPK）, a key enzyme of energy metabolism, were examined by western blot. The activities of AMPK-α1/2 were subject to biochemical assay. Results The swimming training and NE-infusion both evoke a significant elevation of plasma NE, compared with control. The extent of cardiac hypertrophy and tissue fibrosis in NE-infused group are not only obviously higher than those in swimming trained group, but also accompanied by markedly reduced heart function. Specially, continuous NE-infusion also leads to an obvious elevation of AMPK activity. Conclusions Different patterns of catecholamine release might be a crucial factor in regulating the outcome of cardiac remodeling. AMPK might implicate in the adaptative changes of myocardial energy metabolism during the pathological cardiac remodeling.

关 键 词：肾上腺素受体 心脏重塑 腺苷酸-活化蛋白激酶 

分 类 号：R541[医药卫生—心血管疾病]