卡维地洛改善腹主动脉缩窄术后大鼠左室肥厚的实验研究

Pressure overload on left ventricular remodeling: effects of Carvedilol and its mechanism

目的 对照观察卡维地洛 (CAR)等药物干预对压力负荷性左室心肌胶原结合蛋白 (Acollagen bindingprotein ,Colligin)和肌凝蛋白同工酶 (α β MHC)表达的影响 ,探讨卡维地洛改善左室重塑的机制。 方法 将腹主动脉缩窄术 (CAB)后 4周的雄性Wistar大鼠分为CAR、美托洛尔 (MET)、和特拉唑嗪 (TER)干预组与CAB组 ,12周后对有关指标进行检测。结果 术后 16周大鼠左室明显肥厚 ,α MHC β MHCmRNA的比值下降 ,ColliginmRNA表达及CollagenⅠ和Colligin蛋白含量增加 (P <0 .0 5 ) ;卡维地洛能够明显改善左室肥厚 ,美托洛尔次之 ,而特拉唑嗪作用不明显 ;CAR组大鼠左室心肌CollagenⅠ和Colligin蛋白的表达下降 ,α MHC β MHCmRNA表达比值增加 ,ColliginmRNA表达下调 (P <0 .0 5 ) ,但MET组和TER组无显著变化 (P >0 0 5 )。结论 卡维地洛下调心肌细胞外基质蛋白和逆转肌凝蛋白同工酶转换的作用可能与其肾上腺素受体阻滞无关 ,可能部分地与其抗增殖作用可能有关 。

Objective To observe the changes of a collagen binding protein (Colligin) and myosin heavy chain isoform (α/β MHC) gene and protein expression in left ventricular hypertrophy following coarctation of abdominal aorta(CAB) in rats and effects of three kinds of adrenergic receptor blockers: Carvedilol(CAR), metoprolol(MET) and terazosin(TER), to elucidate the effects and new mechanism of CAR on cardiac remodeling regression. Methods Male Wistar rats undergoing coarctation of abdominal aorta were randomly divided into four groups after operation( n =8): CAB, CAR, MET and TER. Hemodynamic, and ventricular remodeling parameters, expressions of Colligin and α/β MHC mRNA, protein expression of type I collagen and Colligin were determined in the experimental animals and sham operation after 12 weeks of treatment. Results Hypertrophy was found in the left ventricle 16 weeks after operation. The ratio of α MHC/β MHC mRNA decreased but expressions of type I collagen proteins and Colligin mRNA/protein increased ( P <0.05). CAR could ameliorate the left ventricular remodeling significantly prior to MET and TER. CAR could also change gene and protein expressions of α MHC/β MHC, type I collagen and Colligin ( P <0.05), but MET and TER had no effect on their expressions ( P >0.1). Conclusion These results indicate that the effects of CAR on left ventricular extracellular matrix proteins and MHC isoform shift regression may be due to the antiproliferative effect, which has nothing to do with this unselective beta adrenergic receptor antagonist. This represents a new mechanism of CAR that may contribute to the observed beneficial effects on congestive heart failure and left ventricular remodeling.