卡维地洛对急性心肌梗死大鼠左室重构的影响

目的建立大鼠急性心肌梗死(acute myocardial infarction,AMI)模型,观察AMI后卡维地洛早期处理对心梗后左室重构的影响。方法雄性Wistar大鼠60只,随机分为假手术组(n=15)、AMI组(n=15)、低剂量卡维地洛组(n=15)和高剂量卡维地洛组(n=15)。建模后2周心肌组织取材,HE、Masson染色病理学检查;免疫组织化学测定心肌组织中毛细血管及抗凋亡、凋亡蛋白表达;建模前1 d及建模后2周心脏超声检查;采用Elisa法对建模前及建模后2周血浆脑钠肽(BNP)水平测定。结果建模后2周,与AMI组比较,卡维地洛组梗死面积减小,梗死区存活心肌细胞数增加,替代性纤维化面积减小,抗凋亡蛋白bcl-xl表达增强,凋亡蛋白Bax表达降低,P<0.05;梗死区及梗死旁区心肌组织中幼稚毛细血管密度增加,上述改变在高剂量药组明显;心脏超声左室收缩末期内径(LVESD)、左室舒张末期内径(LVEDD)、室间隔厚度(IVS)直线小,心率(HR)减慢,左室射血分数(EF)值增加(P<0.05);血浆BNP水平较AMI组明显降低(P<0.05)。结论大鼠AMI后早期应用卡维地洛处理,可减少心肌细胞的凋亡及丢失,减轻AMI后心肌梗死程度,减轻左心室重构,改善AMI后左室功能,延缓心力衰竭的发生。

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

Objective To observe the pathologic variation of left ventricular remodeling in myocardial tissue following AMI by earlier treating with carvedilol in rats.Methods Sixty Wistar rats were randomly divided into sham group,AMI group,low dose carvedilol group and high dose carvedilol group.Rats were administrated carvedilol of 1 mg ·(kg · d)-1 and 2 mg ·(kg · d)-1 following AMI in low dose and high dose carvedilol group.The echocardiography examination was done at 1 day before operation and 2 weeks after operation.The level of BNP in serum was detected by ELISA.After the hearts were harvested at 2 weeks after ligation,histopathological sections and immunohistochemistry of CD31,CD34,bcl-xl and Bax expression were carried out.Results After the administration of carvedilol,the volume of LVESD,LVEDD,IVS and HR were reduced and that of EF was increased and BNP in serum decreased significantly in carvedilol groups compared with AMI group(P<0.05).The expression of CD31,CD34 and bcl-xl increased in both carvedilol groups,while the expression of bax decreased in both carvedilol groups.The area of infarction reduced and residual myocardial increased in infarction region in both carvedilol groups.The high dose carvedilol group was better than the low dose carvedilol group.Conclusions The earlier administration of carvedilol to AMI rats can improve cardiac function and prevent left ventricular remodeling.