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心脏疾病常伴有交感神经系统过度激活及循环系统内儿茶酚胺水平增高,通过激动β-肾上腺素受体引起心脏重塑.β-AR激动剂异丙基肾上腺素常用来制备心脏重塑模型.然而β-AR不同的激动模式,脉冲式的间断激动与慢性持续激动对心脏重塑和心脏功能下降的影响是否不同,尚未见报道.为此,本研究比较了ISO间断给药与持续给药对小鼠心脏重塑和功能的影响.通过两种不同给药模式给予小鼠为期两周的ISO(5mgkg-1天-1)处理:每天皮下注射或通过微渗泵皮下持续输注.心脏重塑和功能通过超声心动图、血流动力学检测及组织学分析进行评价.相关信号分子通过蛋白免疫印迹和实时定量聚合酶链反应进行检测.结果表明,两种不同给药模式引起小鼠心肌肥厚的程度类似(心脏重量/体重比值:皮下注射组增加16%,埋泵组增加19%).但是,与埋泵组相比,ISO皮下注射组引起的心脏纤维化程度更重,并较早发生心脏功能下降.促纤维化因素,包括结缔组织生长因子和NADPH氧化酶亚单位NOX4的表达量在ISO皮下注射组都显著高于埋泵组.综上,与β-AR持续激动相比,β-AR间断激动引起心脏纤维化更重,并更易引起心脏功能失代偿.本研究结果为阐明β-AR不同激动模式在心脏病理重塑中的作用提供了新的视角,并为用肾上腺素受体激动剂复制心脏疾病模型的模式选择提供参考依据.
Cardiac disease is often accompanied by over-activation of the sympathetic nervous system and increased levels of catecholamines in the circulatory system, which cause cardiac remodeling by agonizing the [beta] -adrenoceptor [beta] -AR agonist isoproterenol is commonly used to prepare cardiac remodeling models. It has not been reported that different modes of β-AR, pulsatile intermittent and chronic sustained stimulation have different effects on cardiac remodeling and cardiac function decline.Therefore, this study compared intermittent and intermittent administration of ISO Mouse cardiac remodeling and function The mice were given ISO (5 mg kg-1 day-1) treatment for two weeks by two different modes of administration: subcutaneous injections per day or by subcutaneous infusion of a micro-osmotic pump Cardiac weight The plasticity and function were evaluated by echocardiography, hemodynamic tests and histological analysis.The related signaling molecules were detected by Western blotting and real-time quantitative polymerase chain reaction.The results showed that two different modes of administration induced cardiac muscle Hypertrophy was similar (cardiac weight / body weight ratio: 16% in the subcutaneous injection group and 19% in the buried pump group.) However, compared with the buried pump group, the cardiac fibrosis caused by the ISO subcutaneous injection group The degree of heavier, and earlier heart function decline.Acrosis factors, including connective tissue growth factor and NADPH oxidase subunit NOX4 expression in the ISO subcutaneous injection group were significantly higher than the buried pump group.In summary, and β -AR intermittent activation of β-AR caused cardiac fibrosis heavier and more likely to cause cardiac decompensation.The results of this study provide a new elucidation of the role of different modes of β-AR in cardiac remodeling And provide a reference basis for the mode selection of adrenaline receptor agonist replication heart disease model.