右心衰竭幼龄大鼠B型钠尿肽的变化及卡维地洛的干预作用

B-type natriuretic peptide(BNP) levels and the effects of carvedilol on BNP levels in juvenile rats with right heart failure

目的通过研究右心衰竭幼龄大鼠血清B型钠尿肽(BNP)含量、右室心肌BNP蛋白和BNP mRNA表达的变化及β受体阻滞剂卡维地洛的干预作用,探讨BNP在小儿右心衰竭的诊断和治疗中的意义。方法51只Sprague Dawley4周龄大鼠随机分为4周心衰组、6周心衰组、卡维地洛组、4周对照组和6周对照组。心衰组及卡维地洛组大鼠给予腹腔注射野百合碱(MCT),两个对照组给予腹腔注射生理盐水。至4周形成右心衰竭模型,将4周心衰组和4周对照组幼龄大鼠处死观察心肌病理学变化,同时卡维地洛组开始给予卡维地洛灌胃共14 d,6周心衰组和6周对照组同时等量蒸馏水灌胃至6周。每组存活大鼠测血流动力学和相关生理指标,ELISA法检测血清中的BNP水平,免疫组化法和RT-PCR法检测右室心肌BNP蛋白和BNP mRNA的表达。结果4周心衰组血清BNP浓度、右室心肌中BNP蛋白、BNP mRNA与4周对照组相比均明显升高(P<0.01),6周心衰组上述指标升高更为显著(P<0.01)。血清BNP、心肌BNP蛋白之间具有正相关关系(P<0.01)。卡维地洛组与6周心衰组比较血流动力学改善,右室肥厚减轻,血清BNP浓度、心肌中BNP蛋白和BNP mRNA表达均降低(P<0.05)。结论右心衰竭时BNP可作为诊断和反映心衰严重程度的指标,卡维地洛对治疗压力负荷性右心衰竭有一定作用。

Objective To examined serum B-type natriuretic peptide （BNP） levels and BNP expression of protein and mRNA in the right ventricular myocardium in juvenile rats with right heart failure （ RHF ） and the effects of β- adrenergic receptor blocker carvedilol on serum and myocardial BNP levels in order to investigate the role of BNP in the diagnosis and treatment of RHF. Methods Fifty-one four-week-old Sprague-Dawley rats were randomly assigned to 5 groups： RHF 1, RHF 2, carvedilol-treated RHF, control 1 and control 2. RHF was developed 4 weeks after an intrapefitoneal injection of monocrotaline in the RHF 1, RHF 2 and earvedilol-treated RHF groups. The rats in the RHF 1 and the control 1 groups were sacrificed after the RHF event for observing pathological changes in the myocardium. After the RHF event, the earvedilol-treated group was given intragastrie administration of carvedilol （ 3.5 mg/kg/d） for 2 weeks. The RHF 2 and the control 2 groups were given distilled water of equal dose instead. The rats were sacrificed 2 weeks after earvedilol or distilled water administration. Serum BNP levels were measured using ELISA. BNP protein and mRNA expression in the right ventricular myocardium were measured by immunohistochemistry and RT-PCR, respectively. Haemodynamies and some physiological indexes were measured. Results Serum BNP levels and BNP protein and mRNA expression in the fight ventrienlar myocardium were significantly higher in the RHF 1 group than those in the control 1 group （P 〈 0.01 ）. Serum BNP levels and BNP protein and mRNA expression in the fight ventricular myocardium increased more significantly in the RHF 2 group. There was a positive correlation between serum BNP levels and myocardial BNP protein expression in the RHF group （ r = 0.698, P 〈 0.01 ）. Serum BNP levels and BNP protein and mRNA expression in the carvedilol-treated RHF group were significantly reduced when compared with the RHF 2 group （P 〈 0.05 ）. Carvedilol treatment also resulted in improved hemodynamics and relieved fight ventricular hypertrophy. Conclusions BNP may serve an index for the diagnosis of RHF and the evaluation of severity in children with RHF. Carvedilol shows protections against RHF caused by pressure load.