美托洛尔对异丙基肾上腺素充血性心力衰竭大鼠模型TNF-α的影响.docVIP

美托洛尔对异丙基肾上腺素充血性心力衰竭大鼠模型TNF-α的影响 作者：蔡辉，郭寒，赵智明，蔡佳宇，郭郡浩 【摘要】 目的 探讨美托洛尔对充血性心力衰竭(心衰)大鼠血浆肿瘤坏死因子-α(TNF-α)的影响。方法 雄性SD大鼠80只，随机分为空白组(n=10)及模型组(n=70)，模型组皮下注射异丙基肾上腺素2次(170 mg· kg-1)，6周后应用超声心动图检测，以左室射血分数≤45%确定造模成功，将心衰大鼠模型随机分为心衰对照组(n=13)、美托洛尔组(n=14);18周后使用左心导管进行血流动力学检查，利用放免法检测血浆TNF-α的改变并观察心肌病理形态学特征。结果 与空白组比较，心衰对照组心功能明显恶化，心室质量指数、左心室质量指数及血浆TNF-α显著升高(P0.01 )，心室重构明显;与心衰对照组比较，美托洛尔组心功能明显好转，心室质量指数、左心室质量指数及血浆TNF-α明显降低(P0.05 )，心室重构好转。结论 美托洛尔能改善心功能，逆转心室重构，其作用可能与抑制心衰大鼠血浆TNF-α表达有关。 【关键词】 充血性心力衰竭;异丙基肾上腺素;美托洛尔;大鼠;肿瘤坏死因子-α;心室重构 　　Abstract: Objective To explore the effect of metoprolol on plasma tumour necrosis factor-α (TNF-α) in rats with congestive heart failure (CHF). Methods 80 male SD rats were randomly allocated to the isoproterenol (ISO)-induced heart failure group (n=70) recEiving a subcutaneous injection of ISO (170 mg per kilogram of body wEIght) twice and the healthy normal group (n=10) receiving a subcutaneous injection of 0.25 ml of normal saline twice. At the 6th week, the left ventricular ejection fractions (LVEF) were measured by echocardiogram, the remaining rats, with a LVEF≤45%, were randomly divided into two groups: heart failure control group (n=13), metoprolol group (n=14，8 mg/kg-1· d-1, i. g., ). At the 18th week, the hemodynamic parameters were detected, including HR, LVEDP, LVSP and ±dp/dtmax; LVWI was measured after LV morphopathological examination. TNF-α in plasma was examined by radioimmunoassay. Results ①Compared with the normal group, the heart function significantly deteriorated; VWI, LVWI and the plasma TNF-α significantly increased (P0.01) in the heart failure control group. ②Compared with the heart failure control group, the heart function markedly improved, and the VWI, LVWI and the plasma TNF-α decreased significantly (P0.05 ) in the metoprolol group, with an improved ventricular remodeling. Conclusion Metoprolol can inhibit the plasma TNF-α, improve heart function and reverse ventricular remodeling with CHF. Its effect might be involved in the inhib