卡维地洛对大鼠急性心肌梗死后心肌重塑的影响

目的:建立大鼠急性心肌梗死(AMI)模型,用组织学的方法,观察AMI后早期卡维地洛处理,心肌重塑相关指标的变化。方法:结扎左冠状动脉前降支复制AMI模型。将大鼠随机分为假手术(S)组、心肌梗死组(I)、高剂量卡维地洛组(H)2mg·kg-1·d-1和低剂量卡维地洛组(L)1mg·kg-1·d-1。实验动物存活2h后,药物组每日口服不同剂量卡维地洛。各组均于用药后2周观察光镜及透视电镜下左心室心肌组织学改变并进行定量分析。结果:药物组心肌梗死面积明显减小(I组、L组和H组分别为0.149±0.010、0.039±0.009和0.028±0.004),与I组比较,P均<0.05,残存心肌纤维断裂及排列紊乱程度减轻;梗死区、非梗死区内心肌细胞退行性改变减轻,心肌细胞线粒体以增生、肿胀为主,线粒体膜完整,细胞核增大。心肌间质中幼稚毛细血管密度增加(I组、L组和H组分别为4.36±0.010,7.22±0.009和9.86±0.004),与I组比较,P均<0.05,上述改变在H组更明显。结论:AMI后卡维地洛早期干预,可改善AMI后心肌重塑水平并具有剂量依赖性。卡维地洛的线粒体保护作用可能是其抑制AMI后心肌重塑、改善AMI患者预后的细胞学机制之一。

Effects of treating with carvedilol on myocardial remodeling following acute myocardial infarction in rats

Objective：To observe the pathologic variation of myocardial tissue following acute myocardial infarction by earlier treating with Carvedilol. Method： Established acute myocardial infarction model by ligation of left anterior descending coronary artery（LADCA） in rats. Animals were randomly divided into sham group（without ligation of LADCA）, AMI group （ligating LADCA.）, high-dose Carvedilol group （administrating Carvedilol with 2 mg·kg^- 1· d^-1 after 2 h following AMI）, low-dose Carvedilol group（ administrating Carvedilol with 1 mg· kg^- l· d^- 1 after 2 h following AMI）. After 2 wks of Carvedilol administration, the pathologic variation of myocardial specimens of each group were examined by light microscope and transmission electron microscope and related quantitative analysis were proceed. Result：Compared with AMI group, the areas of myocardial infarction in both carvedilol groups （low- dose and high-dose） were reduced significantly,from 0.149 ± 0.010 to 0.039 ±0.009 and 0.028±0.004 （ P 〈 0.05）, and decreased degree of abruption and disorganized of myocardial fibers in residual myocardium were also observed. Unimpaired mitochondria membranes, increased interstitium immature capillary density, mitochondria hyperplasy and swelling and enlarged cellular nucleus were found in myocardium and in myocardial cells under light microscope and electric microscope examination following carvedilol treatment. All variations above showed significant differences and were more obvious in high- dose Carvedilol group. Conclusion：The earlier treating with carvedilol for AMI rats can improve myocardial remodeling and the effects are dose dependent. We suppose that the mitochondrial protective effects of carvedilol may be one of the cellular mechanism in its effects on myocardial remodeling suppressing and AMI outcome improving.