不同肾上腺素能受体阻滞剂对改善压力负荷大鼠左室重塑的作用  

Effects of different adrenergic receptor antagonists on left ventricular remodeling to pressure overload

作　　者：胡琴[1] 李隆贵[1] 耿昭华[1] 吴立荣[2] 方颖[2] 

机构地区：[1]第三军医大学新桥医院心内科,重庆现在400037 [2]贵阳医学院附属医院心内科

出　　处：《中华心血管病杂志》2003年第5期373-376,共4页Chinese Journal of Cardiology

摘　　要：目的　比较卡维地洛、美托洛尔和特拉唑嗪对压力超负荷性左室心肌胶原结合蛋白(collagen bindingprotein ,Colligin)和肌球蛋白同工酶 (α/ β MHC)表达的影响 ,探讨卡维地洛改善左室重塑的新机制。方法　将腹主动脉缩窄术后 4周的雄性Wistar大鼠随机分为腹主动脉缩窄术、卡维地洛、美托洛尔、特拉唑嗪 4组 (n =8)。治疗 12周后 ,观察各组大鼠各项指标的变化。结果　术后 16周大鼠左室明显肥厚 ,α/ β MHCmRNA的比值下降 ,ColliginmRNA表达及Ⅰ /Ⅲ型胶原和Colligin蛋白含量增加 (P <0 0 5 ) ;药物治疗 12周后 ,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 ;卡维地洛组大鼠左室心肌Ⅰ /Ⅲ型胶原和Colligin蛋白的表达下降 ,α/ β MHCmRNA表达比值增加 ,ColliginmRNA表达下调 (P <0 0 5 ) ,但美托洛尔组和特拉唑嗪组无此变化 (P >0 0 5 )。结论　卡维地洛与美托洛尔均能明显改善左室肥厚 ,而非选择性 β肾上腺素能受体阻滞剂卡维地洛更能下调心室细胞外基质蛋白和逆转肌球蛋白同工酶转换 ,其作用机制有待进一步确定。Objective To study the changes of a collagen-binding protein (Colligin) and myosin heavy chain isoform(α/β-MHC) gene and protein in left ventricular hypertrophy subsequent to coarctation of abdominal aorta in rats and the effects of three kinds of adrenergic receptor blockers: Carvedilol(CAR), Metoprolol(MET) and Terazosin(TER) on those changes,and to elucidate the effects and new mechanism of CAR on cardiac remodeling regression. Methods A model of hypertrophy induced by coarctation of abdominal aorta(CAB)was used in this study. Thirty two male wistar rats were divided randomly into four groups( n =8): CAB, CAR, MET and TER 4 week after CAB operation. Treatment time was 12 weeks. Hemodynamics, ventricular remodeling parameters, expressions of Colligin and α/β-MHC mRNA, protein expression of Collagen Ⅰ/Ⅲ and Colligin were investigated in the four groups and sham operation group. Results Left ventricular hypertrophy was observed clearly 16 weeks after operation. The ratio of α/β-MHC mRNA decreased, while expressions of Collagen Ⅰ/Ⅲ proteins and Colligin mRNA/protein increased( P <0.05). CAR could ameliorate left ventricular remodeling significantly prior to MET and TER. CAR could also change the expressions of α/β-MHC, Collagen Ⅰ/Ⅲ and Colligin in both gene and protein levels( P <0.05), while MET and TER had no effect on them( P>0.05). Conclusions These results indicated that the effects of CAR on extracellular matrix proteins and MHC isoform shift regression of left ventricle may be due to antiproliferative or antioxidative mechanism, which was independent of beta-adrenergic receptor antagonist. This new mechanism of CAR may contribute to the observed beneficial effects on congestive heart failure and left ventricular remodeling.

关 键 词：肾上腺素能受体阻滞剂 卡维地洛 美托洛尔 特拉唑嗪 压力超负荷性 左室心肌胶原结合蛋白 

分 类 号：R541[医药卫生—心血管疾病]