应激山羊心肌交感神经信号细胞传导过程及干预研究

Study of cellular transmission pathway of cardiac sympathetic nerve signals in a stressed goat model

目的:研究急性应激山羊心律失常发生以及心肌β肾上腺素能受体(-βAR)密度、腺苷酸环化酶(AC)活性和环磷酸腺苷(cAMP)水平的变化,探讨应激状态下交感神经兴奋的细胞信号传入过程。方法:雄性山羊15只,随机分为对照组、应激组和倍他乐克干预组(各5只)。采用声、光复合刺激建立急性应激模型。24 h Holter记录心律失常,留取心房、心室全层肌组织,应用放射性配基受体结合实验、放射免疫分析等方法检测心肌β-AR、AC活性和cAMP水平。结果:①应激诱发情况应激组和干预组山羊出现明显应激表现(燥动不安、敌意,心律失常增多);②β-AR密度与对照组心房、心室肌β-AR密度相比,应激组和干预组显著增高(P<0.05,P<0.01),应激组和干预组间无显著性差异;3组平衡解离常数(KD值)无显著差别;③AC活性应激组心房、心室肌AC水平高于对照组和干预组(P<0.05,P<0.01),干预组高于对照组(P<0.05);④cAMP含量与对照组心房、心室肌cAMP含量相比,应激组和干预组显著增高(P<0.05,P<0.01),干预组cAMP水平低于应激组(P<0.05)。结论:在本研究建立的应激模型中,完整的β-AR-AC-cAMP途径参与了急性应激时交感神经兴奋引发的生物效应。倍他乐克通过对上述信号传入途径的抑制,部分阻断交感兴奋所致的不良反应。

AIM： To investigate the genesis of arrhythmias and changes of density of β-AR, AC activity and cAMP level of myocardia in a stressed goat mode and to clarify the pathway of sympathetic signals across myocardial membrane. METHODS： Fifteen adult male goats were randomly divided into control, stress and metoprolol groups. Twenty four hour noise and flash light stimulation were used to establish the acute stress model and 24 h Hoher monitoring was performed. Subsequently, animals were anesthetized and killed by bloodletting through the aorta, and myocardial tissues were kept for preparing membrane samples. β-AR density, AC activity and cAMP level were measured by radioligand binding assay and radioimmunoassay. RESULTS： Obvious stress responses occurred in stress and metoprolol groups. β-AR density increased similarly （P 〈0. 05, P 〈 0. 01 ） in both groups and were higher than in control group （P 〈0. 05, P 〈0.01 ）. No significant difference was observed in KD values among the three groups. AC activity and cAMP level in stress group were higher than in control and metoprolol groups （P 〈 0.05, P 〈0. 01 ） , and these indices in metoprolol group were also higher than in control group （P 〈 0. 05 ）. CONCLUSION： Our study shows that intact β-AR-AC-cAMP pathway-mediated biological reactions result from sympathetic activation, and metoprolol may inhibit the signal transmitting pathway and partially block adverse effects of sympathetic activation.