卡维地洛和美托洛尔对大鼠急性心肌梗死后胶原重构影响的对比研究

目的　对比研究非选择性 β受体阻滞剂卡维地洛及选择性 β1 受体阻滞剂美托洛尔对大鼠心肌梗死后胶原的影响 ,以了解卡维地洛改善心室重构及心功能的机制。方法　将梗死后 4 8h存活大鼠分为心肌梗死对照组、美托洛尔组 (15mg·kg- 1 ·d- 1 )、低剂量卡维地洛组 (1mg·kg- 1 ·d- 1 )和高剂量卡维地洛组 (10mg·kg- 1 ·d- 1 )。另设假手术组。给药 6周后 ,测量血流动力学参数及心功能。取血测量血浆内皮素及血管紧张素Ⅱ。测量心肌梗死区及非梗死区的总间质胶原容积分数 (ICVF)及Ⅰ、Ⅲ型胶原的ICVF。结果　美托洛尔及卡维地洛均可减低左心室舒张末压、增加左心室内压最大上升和下降速率 ,以高剂量卡维地洛组效果最好。与心肌梗死对照组比较 ,高剂量的卡维地洛可减轻心肌非梗死区尤其是右心室的ICVF及Ⅰ、Ⅲ型胶原的ICVF。低剂量卡维地洛及美托洛尔对间质胶原影响不明显。结论　卡维地洛可抑制非梗死区胶原增生 ,减少心肌纤维化 ,而美托洛尔无此作用。卡维地洛对心肌纤维化的抑制可能较美托洛尔能更好地改善心肌梗死后心室重构及心功能

Effect of carvedilol in comparison with metoprolol on myocardial collagen remodeling after acute myocardial infarction in the rats

Objective To compare the effects of two different beta-blockers,carvedilol and metoprolol,on myocardial collagen deposition during healing after MI and to explore the mechanism of carvedilol in improving LV remodeling and myocardial function.Methods Forty-eight hours after the AMI,the first group received distilled water as AMI control group,and the other three groups received metoprolol(15 mg·kg -1·d -1),low-dose carvedilol(1 mg·kg -1·d -1) and high-dose carvedilol(10 mg·kg -1·d -1).The sham-operated rats received distilled water.After six weeks of treatment,the hemodynamics,myocardial function and plasma AngII and ET-1 were measured.The total collagen and collagen types Ⅰ and Ⅲ in the infarcted region as well as the noninfarcted region were measured.Results Both carvedilol and metoprolol could reduce the LVEDP and elevated ±dP/dt max.The high-dose carvedilol had the best efficacy and could reduce the total interstitial collagen volume fraction(ICVF)in noninfarcted region,especially in the right ventricle,and type-Ⅰ and Ⅲ ICVF.But the low-dose carvedilol and metoprolol had no effects.Conclusions Carvedilol can reduce the collagen deposition in noninfarcted area,while metoprolol cannot.The effect of carvedilol in reducing fibrosis perhaps can produce better therapeutic efficacy in improving LV remodeling and myocardial function after MI.