呋塞米对心衰大鼠心功能及心肌纤维化的影响

Effect of furosemide on cardiac function and myocardial fibrosis in heart failure rats

目的探讨呋塞米对心肌梗死后心力衰竭大鼠心功能及心肌纤维化的影响。方法采用结扎冠状动脉左前降支构建心肌梗死后心力衰竭大鼠模型。术后2周将34只大鼠随机分为3组:假手术组(10只,生理盐水)、心衰对照组(12只,生理盐水)及呋塞米组[12只,20 mg/(kg·d)]。药物干预4周后分别行超声心动图、血流动力学、心肌Masson染色,测定胶原容积分数(CVF)、血浆血管紧张素Ⅱ(AngⅡ)、醛固酮以及心肌转化生长因子β1(TGF-β1)和胶原纤维Ⅲ(CollagenⅢ)mRNA的表达。结果与心衰对照组比较,呋塞米组的左室舒张末期压(LVEDP)明显升高(P<0.05),而射血分数(EF)升高不明显。呋塞米组的AngⅡ、醛固酮、CVF及TGF-β_1和Collagen Ⅲ mRNA的表达均显著升高(P<0.05)。结论呋塞米能进一步激活心衰大鼠的肾素-血管紧张素-醛固酮系统(RAAS),进而升高TGF-β水平,促进心肌纤维化重构,最终加剧心功能的恶化。

Objective To explore the effect of furosemide on cardiac function and myocardial fibrosis in rats with heart failure after myocardial infarction.Methods Heart failure was produced by ligation of the left anterior descending coronary artery in rats.Two weeks after the ligation 34 rats were randomly divided into 3 groups：Sham operation group（n = 10）,heart failure group（n = 12） and furosemide group（n = 12）.Echocardiography,hemodynamic measurements,Masson＇s trichrome staining and collagen volume fraction,plasma angiotensin Ⅱ and aldosterone levels the mRNA expression of TGF-β and Collagen Ⅲ in the myocardium were detected at four weeks after drug intervention.Results Compared with the heart failure group the left ventricular end diastolic pressure（LVEDP） in furosemide group was significantly higher（P〈0.05） but no significant difference was found in ejection fraction（EF）.In addition plasma angiotensin Ⅱ and aldosterone levels,myocardial collagen volume fraction and the mRNA expression of TGF-β and Collagen Ⅲ increased significantly（P〈0.05）.Conclusion Furosemide can further activate the heart failure RAAS,and increase TGF-β level,promote the reconstruction of myocardial fibrosis,ultimately exacerbate the deterioration of cardiac function.