阿替洛尔对小鼠心肌肥厚干预作用的研究

Effect of atenolol on cardiac hypertrophy in mice

目的:观察β1受体阻滞剂阿替洛尔(atenolol,ATE)对主动脉弓缩窄术(aortic arches constriction,AAC)诱导的C57BL小鼠心肌肥厚模型的治疗作用。方法:通过AAC建立心肌肥厚小鼠模型,将24只雄性C57BL小鼠随机分为正常对照组、假手术(Sham)组、AAC组和AAT+ATE组,每组6只小鼠(n=6)。给予ATE 4周后,进行心脏超声检查,并测量心脏质量/体质量(HW/BW)、左心室质量/体质量(LVW/BW)、左室舒张末期内径(LVEDD)、左室收缩末期内径(LVEDS)、左室射血分数[LVEF(%)]和短轴缩短率[FS(%)]。应用PCR检测心肌组织中心房钠尿肽(ANP)、脑尿钠肽(BNP)和肌球蛋白重链(α-MHC)基因表达的水平,并行病理学检查。结果:与AAC组比较,正常对照组、Sham组和AAC+ATE组的LVEDD分别降低24.9%、17.7%和18.2%,LVEDS分别降低32.9%、34.1%和26.3%;LVEF(%)分别提高65.6%、75.8%和49.5%,FS(%)分别提高79.7%、100.0%和62.6%(均P<0.05);AAC+ATE组与AAC组相比,LVM/BW和心肌细胞平均横截面积均明显降低(P<0.01);而与正常对照组相比,细胞平均面积明显增大(P<0.05)。AAC+ATE组中ANP、BNP和α-MHC的表达水平显著低于AAC组(P<0.05)。结论:通过阻断β1受体ATE,可以对压力超负荷等原因诱导的心肌肥厚发挥治疗作用。

AIM： To observe the effect of the β1-receptor blocker,atenolol,on transverse aortic constriction（AAC）-induced myocardial hypertrophy.METHODS： Twenty-four male C57BL mice were randomly divided into four groups： normal control group,sham group,AAC operation group and AAC plus atenolol treatment group.After 4 weeks of treatment,echocardiogram was performed to assess cardiac function changes,heart weight to body weight ratio（HW/BW）,heart weight/tibial length,left ventricular ejection fraction（LVEF%） and LV fractional shortening（FS%）.Expression levels of ANP,BNP and β-MHC mRNAs in heart tissues and the size of cardiomyocytes were also measured using PCR and pathological techniques.RESULTS： Compared with those in AAC group,LVEDd decreased 24.9%,17.7% and 18.2% and LVEDs decreased 32.9%,34.1% and 26.3%,respectively,in normal control group,sham group and atenolol group,whereas EF increased 65.6%,75.8% and 49.5% and FS increased 79.7%,100.0% and 62.6%,respectively（P〈0.05）.LVM/BW and cardiac myocyte cross-sectional area showed a decrease in atenolol group compared with that in AAC group（P〈0.01）,but they still increased significantly compared with those in the normal control group.Expressions of ANP,BNP and α-MHC mRNAs in atenolol group were lower than those in AAC group（P〈0.05）.CONCLUSION： Atenolol can intervene during the progress of pressure overload-induced myocardial hypertrophy in C57BL mice.