美托洛尔对大鼠急性心肌梗死后左心室重构的影响

Effects of Metoprolol on Left Ventricular Remodeling after Acute Myocardial Infarction in Rats

目的观察美托洛尔对大鼠急性心肌梗死(AMI)后左心室重构(VR)的影响,并初步探讨其作用机制。方法将大鼠随机分为美托洛尔治疗组、模型组及假手术组。结扎美托洛尔治疗组和模型组大鼠左冠状动脉前降支,假手术组给予假手术。美托洛尔治疗组于术后24 h灌胃给予美托洛尔10 mg.kg-1.d-1,其他两组灌胃给予等量0.9%氯化钠溶液。手术4周后,采用高频彩色多普勒超声观察各组大鼠左室舒张末期内径(LVDD)、左室舒张末期容积(LEDV)、左室质量指数(LVMI)、射血分数(EF)、短轴缩短率(FS)变化,病理切片观察大鼠心肌细胞和细胞间质变化。结果与假手术组比较,模型组大鼠LVDD、LEDV、LVMI均显著增加,EF、FS等显著降低,光镜下心肌细胞肥大,间质增生明显;与模型组比较,美托洛尔治疗组LVDD、LEDV、LVMI降低,EF、FS升高,均差异有统计学意义(均P<0.05)。结论美托洛尔对AMI大鼠左心室重构具有治疗作用,其作用机制可能与纠正血流动力学异常和神经内分泌异常、降低交感神经过度再生有关。

Objective To investigate the effects and mechanism of metoprolol on left ventricular remodeling（LVR） after acute myocardial infarction（AMI） in rats. Methods The Wistar rats were randomly assigned to three groups： AMI control（n=9）,metoprolol treatment（n=9） and sham-operated group（n=9）.The rats of AMI control and metoprolol treatment were ligated in the left anterior descending coronary artery;the sham-operated rats were not ligated.The metoprolol group was given with metoprolol 10 mg·kg-1·d-1,and the other two groups with the same dose of 0.9% natrium chloride.Four weeks later,the left ventricular end-diastolic dimension（LVDD）,left ventricular end-diastolic volume（LEDV）,left ventricular mass index（LVMI）,ejection fraction（EF） and fractional shortening（FS） of each rat was detected by echocardiogram.Myocardial cell and interstitial tissue were observed by HE stain. Results Compared with those in the sham-operated group,the LVDD,LEDV and LVMI in AMI group were all significantly increased（P0.05）.The parameters in AMI including EF and FS were all significantly alleviated（P0.05）.Meanwhile,cardiac myocyte hypertrophy was found by HE stain.However,in metoprolol group,the EF and FS were improved in comparison to those in AMI group. Conclusion Metoprolol had a therapeutic effect on LVR after AMI,the mechanism of which should be associated with inhibiting sympathetic nerve hyperplasia and reforming anomalies of neuroendocrine and hemodynamics.