美托洛尔对异丙基肾上腺素诱导心力衰竭大鼠心肌细胞凋亡的影响

Effect of metoprolol on myocardial cell apoptosis in rats with ISO-induced congestive heart failure

目的探讨美托洛尔对充血性心力衰竭大鼠心肌细胞凋亡的影响。方法实验选用清洁级雄性SD大鼠60只,随机分为空白组(n=15),模型组(n=45)皮下注射异丙基肾上腺素2次(170 mg/kg),6周后应用超声心动图检测,以左室射血分数(LVEF)小于或等于45%确定造模成功,将心力衰竭大鼠模型随机分为对照组(n=13)、美托洛尔治疗组(n=14)8 mg.kg-1.d-1,18周使用左心导管进行血流动力学检查,并利用琼脂糖凝胶电泳法检测DNA断片化和免疫印迹分析法检测Bcl-2、Bax、caspase-9和caspase-3的表达。结果(1)与空白组相比,对照组血流动力学指标明显恶化,心室质量指数(VWI)、左心室质量指数(LVWI)显著升高,心肌细胞凋亡率增加;(2)与对照组比较,美托洛尔组心率(HR)、左心室舒张末压力(LVEDP)、VWI及LVWI明显降低(P<0.05)和±dp/dtmax明显升高(P<0.05),左心室重量指数明显降低(P<0.05),心肌细胞凋亡率下降。结论美托洛尔能抑制心力衰竭大鼠心肌细胞凋亡,改善心功能,逆转心室重构。

Objective To explore the effect of metoprolol on myocardial cell apoptosis in rats with heart failure.Methods 60 male Sprague-Dawley rats were randomly allocated to the ISO-induced chronic heart failure group（n= 45） receiving two subcutaneous injections of 170 mg ISO per-kilogram of body and the healthy normal group（NOR group,n= 15） receiving two subcutaneous injections of 0.25 mL normal saline.At 6-week,the left ventricular ejection fraction（LVEF） was measured by echocardiogram,the remaining rats,with left ventricular ejection fraction≤45%,were randomly divided into two groups：control group（n=13）,metoprolol group（8 mg·kg-1· d-1,n=14）,the drugs were given by gastric perfusion.At 18-week,then the hemodynamic parameters were detected,including heart rate,left ventricular end diastolic pressure,LV systolic pressure,LVWI was measured after LV morphopathological examination.The DNA fragmentation was detected by agarose gel electrophoresis method and the Bax,cleaved caspase-9 and cleaved caspase-3 were detected by Western blot analysis method.Results（1）Compared with the NOR group,the HR,LVEDP,LVWI and the DNA fragmentation Bcl-2,Bax,cleaved caspase-9 and cleaved caspase-3 in the myocardial cells were significantly increased（P〈0.01）.But LVSP and ±dp/dtmax and Bcl-2 were significantly decreased in the CON group.（2）Compared with the CON group,the HR,LVEDP,LVWI and the DNA fragmentation Bcl-2,Bax,cleaved caspase-9 and cleaved caspase-3 in the myocardial cells were significantly decreased.The LVSP and ±dp/dtmax and Bcl-2,significantly increased（P〈0.01） in the metoprolol group.Conclusion Metoprolol can inhibit myocardial cell apoptosis,improve heart function and reverse ventricular remodeling in rats with congestive heart failure.