美托洛尔对心力衰竭大鼠心肌一氧化氮水平的影响

Metoprolol reduces nitric oxide in the myocardium of rats with isoproterend-induced congestive heart failure

目的目前,一氧化氮(nitric oxide,NO)与心力衰竭的心室重塑的研究多有报道;文中通过观察美托洛尔对充血性心力衰竭(congestive heart failure,CHF)大鼠心肌NO的影响,探讨美托洛尔影响CHF大鼠心室重塑的机制。方法选用清洁级雄性SD大鼠80只,随机分为空白组(n=10),模型组70只皮下注射异丙基肾上腺素(isoproterend,ISO)2次(170mg/kg),6周后应用超声心动图检测,以左心室射血分数(left ventricular ejection fraction,LVEF)≤45%确定造模成功,将模型随机分为心力衰竭代偿组,心力衰竭组;再将心力衰竭组随机分为心力衰竭失代偿组和美托洛尔组,18周使用超声心动图检测,利用硝酸还原酶法检测心肌NO浓度,并取心肌观察病理形态学特征。结果与空白组相比,心力衰竭代偿组和心力衰竭失代偿组心功能指标显著恶化,心肌NO、心室重量指数明显升高(P<0.05);与心力衰竭失代偿组相比,美托洛尔组心功能指标显著好转,心肌NO、心室重量指数明显降低(P<0.05)。结论美托洛尔能够降低实验性心力衰竭大鼠心肌NO水平,改善心室重塑及心功能。

Objective Several studies on the relationship between nitric oxide（NO） and ventricular remodeling have been reported recently.The authors aimed to investigate the mechanism of metoprolol acting on ventricular remodeling in rats with congestive heart failure（CHF） by observing the effect of metoprolol on NO in the myocardium of isoproterend（ISO）-induced CHF rat models.Methods Eighty male SD rats were randomly allocated to an ISO-induced CHF group（ISO,n=70） and a normal control group（NOR,n=10）,the former receiving 2 subcutaneous injections of ISO at 170 mg/kg,and the latter 2 subcutaneous injections of 0.25 ml normal saline.Six weeks later,the left ventricular ejection fraction（LVEF） was measured by echocardiography,the rats with an LVEF≤45% were randomly divided into a compensation group（COMP） and a heart failure group,and the latter again randomly assigned to a decompensation heart failure group（DECOMP） and a metoprolol group（MET）.At 18 weeks,heart function parameters,including LEVF,FS,LVEDD,LVESD and LVWI,were obtained following LV morphopathological examination,and NO was detected by the nitrate reductase method.Results Compared with the NOR group,heart function was markedly decreased,but LVWI,pathological scores and NO in the myocardium significantly increased（P0.05） in the DECOMP and COMP groups.While the metoprolol group showed a distinct increase in heart function and a significant decrease in LVWI,pathological scores and NO（P0.05） in comparison with the DECOMP and COMP groups.Conclusion Metoprolol can down-regulate NO in the myocardium and improve ventricular remodeling and heart function in the rat models of ISO-induced CHF.