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

摘要:

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 Dawley 4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BNPmRNA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。［中国当代儿科杂志，2009，11（7）：571-576］

Abstract:

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 intraperitoneal injection of monocrotaline in the RHF 1, RHF 2 and carvedilol-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 carvedilol-treated group was given intragastric 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 carvedilol 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. Haemodynamics and some physiological indexes were measured. RESULTS: Serum BNP levels and BNP protein and mRNA expression in the right ventricular 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 right 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 right 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.［Chin J Contemp Pediatr, 2009, 11 (7):571-576］