神经调节蛋白1β与卡托普利对慢性心衰大鼠心肌纤维化及转化生长因子β1的影响

目的:探讨神经调节蛋白1β(neuregulin-1β,NRG-1β)与卡托普利联合应用对慢性心力衰竭大鼠心肌纤维化及转化生长因子β1(transforming growth factor-β1,TGF-β1)表达的影响。方法:将青年雄性SpragueDawley大鼠随机分为假手术组、心衰组、NRG组、卡托普利组和联合用药组,采用腹主动脉-下腔静脉穿刺造瘘法制备心衰模型。通过超声心动图评价大鼠心功能;Masson染色检测心肌纤维化程度,并计算胶原容积分数(collagen volume fraction,CVF);放射免疫法检测血浆中血管紧张素II(Ang II)的浓度;Western blot检测各组大鼠左心室心肌组织中TGF-β1和α-平滑肌肌动蛋白(α-SMA)的蛋白表达水平;透射电镜观察左室心肌的超微结构。结果:与心衰组比较,NRG组、卡托普利组及联合用药组左心室舒张末直径和心肌纤维化程度明显降低,射血分数明显升高(P0.05);TGF-β1和α-SMA蛋白表达明显降低(P0.05);电镜下显示,NRG组、卡托普利组及联合用药组心肌纤维化程度较心衰组明显减轻,而与NRG组和卡托普利组相比,联合用药组效果更加显著(P0.05)。结论:神经调节蛋白1β与卡托普利单用及联合应用均可有效改善心功能、抑制心肌纤维化,且联合用药的疗效优于单独用药。

Effect of neuregulin-1β and captopril on myocardial fibrosis and TGF-β1 in rats with chronic heart failure

AIM: To study the effects of neuregulin-1β (NRG-1β) and captopril alone and in combination on myocardial fibrosis and transforming growth factor-β1 (TGF-β1) expression in the rats with chronic heart failure. METHODS: Young male Sprague-Dawley rats were randomly divided into sham group, heart failure group, NRG group, captopril group and combined treatment group. The volume-overloaded heart failure model in the rats was established by aortocaval fistula. The cardiac function was evaluated by determining the changes of echocardiography. The degree of myocardial fibrosis was detected by Masson staining. The protein levels of TGF-β1 and α-smooth muscle actin (α-SMA) in left ventricular tissue were detected by Western blot. Ultrastructure of left ventricular myocardium was observed under transmission electron microscope (TEM). RESULTS: The left ventricular end-diastolic dimension, the protein levels of TGF-β1 and α-SMA, and the degree of myocardial fibrosis were significantly lower, while ejection fraction was significantly higher in NRG group, captopril group and combined treatment group than those in heart failure group (P<0.05). Under TEM, the myocardial fibrosis degree in NRG group, captopril group and combination group was significantly alleviated compared with heart failure group. The effect in combined treatment group was more significant than that in NRG group and captopril group (P<0.05). CONCLUSION: Neuregulin-1β and captopril alone and the combination of them effectively improve the cardiac function and inhibit myocardial fibrosis in chronic heart failure rats. The therapeutic effect of combination of NRG-1β and captopril is better than that of NRG-1β and captopril alone.