培哚普利对心肌梗死大鼠左室重构和心肌组织osteopontin蛋白表达的影响

Effects of perindopril on left ventricular remodeling and myocardial osteopontin expression in rats with myocardial infarction

目的观察血管紧张素转换酶抑制剂培哚普利对心肌梗死大鼠左室重构和心功能的影响,并探讨osteopontin蛋白在其中的作用。方法将成年雄性SD大鼠随机分为3组:假手术组,心肌梗死盐水组和心肌梗死培哚普利组。后两组动物在冠状动脉左前降支结扎第2天起给予生理盐水或者培哚普利灌胃,1次/d。4周后测定有创左室血流动力学,超声心动图测量左室内径和射血分数,组织学方法检测非梗死区心肌细胞直径和胶原纤维沉积,Westernblot检测心肌组织osteopontin蛋白表达水平。结果与假手术组相比,所有心肌梗死大鼠(盐水组和培哚普利组)均出现显著的左室收缩和舒张功能障碍,表现为LVEF、LVSP和±dp/dtmax下降,LVEDP显著升高。同时左室重量与体质量比值升高,LVEEDD和LVESD增大,非梗死区心肌细胞横径增加,心肌间质胶原纤维沉积增加,提示显著的左室重构。与盐水组相比,培哚普利治疗显著改善心肌梗死大鼠心功能,预防左室扩大,减轻非梗死区心肌细胞肥大和心肌间质胶原纤维沉积。Westernblot未检测到osteopontin蛋白在假手术大鼠心肌组织表达,在心肌梗死大鼠心肌组织有大量osteopontin蛋白表达,该上调的蛋白能被培哚普利治疗显著抑制。结论培哚普利抑制心肌梗死大鼠左室重构,改善心功能,可能与其抑制osteopontin蛋白表达有关。

Objective To observe the effects of perindopril on left ventricular remodeling and myocardial osteopontin expression in rats with myocardial infarction （MI）. Methods Male adult SD rats were randomly divided into sham-operation group, MI-saline group and MI-perindopril group, and in the latter two groups, ligation of the left anterior descending artery was performed to establish rat models of myocardial infarction and perindopril （2 mg/kg daily） or saline was administered since the next day of MI. Four weeks later, the left ventricular diameter （LVEDD and LVESD） and left ventricular ejection fraction were estimated with echocardiography, and the left ventricular systolic pressure （LVSP）, left ventricular end-diastolic pressure （LVEDP） and ±dp/dtmax was obtained via hemodynamic measurement, with also evaluation of the cardiac myocyte diameter and interstitial fibrosis infiltration with histological methods. Western blotting was performed to detect the expression level of myocardium osteopontin protein. Results Compared with the sham-operation group, all MI rats developed significant systolic and diastolic dysfunction, as indicated by decreased LVEF, LVSP and ±dp/dtmax, as well as increased LVEDP. MI rats showed significantly dilated left ventricles and higher ventricular weight/body weight ratio, significantly increased cardiomyocyte diameter and marked interstitial fibrosis in the non-infarction area. Perindopril treatment partially prevented cardiac dysfunction and left ventricular remodeling as indicated by the above indices. No osteopontin was detected in the myocardium of sham-operation rats, and in MI rats, high level of osteopontin expression, as detected in MI-saline group, was significantly inhibited by perindopril treatment. Conclusion Perindopril treatment can significantly inhibit left ventricular remodeling and myocardium osteopontin expression in rats with MI.