盐酸伊伐布雷定对慢性心力衰竭大鼠心肌纤维化的影响
Effects of ivabradine hydrochloride on myocardial fibrosis in rats with chronic heart failure

目的:研究盐酸伊伐布雷定(Iva)对慢性心力衰竭(CHF)大鼠心肌纤维化的影响。方法:将44只Wistar大鼠随机分为假手术组、模型组、Iva组、阳性对照(倍他乐克)组。除假手术组外,其余3组大鼠均采用缩窄腹主动脉的方法构建CHF模型,术后饲养至第6周末测定大鼠心脏左室舒张末压力(LVEDP),LVEDP≥15 mmHg为建模成功的标准。建模成功后,Iva组每d灌胃10 mg/kg Iva,倍他乐克组每d灌胃10 mg/kg倍他乐克; 假手术组和模型组每d灌胃10 mg/kg生理盐水; 饲养至第12周末检测LVEDP,心肌组织中超氧化物歧化酶(SOD)的含量,结缔组织生长因子(CTGF)表达水平,HE和masson染色观察判断心肌纤维化程度。结果:与假手术组相比,模型组大鼠LVEDP增大,心肌组织中SOD含量减少,CTGF表达水平升高(P<0.01),心肌纤维化程度严重。与模型组比较,Iva组大鼠LVEDP减小,SOD含量增加,心肌组织中CTGF表达水平降低(P<0.01),心肌纤维化程度减轻。结论:Iva可以降低CHF大鼠心脏LVEDP,增加心肌组织中SOD含量,抑制心肌组织中CTGF表达,从而对MF产生抑制作用。
Aim: To investigate the effects of ivabradine hydrochloride(Iva)on myocardial fibrosis(MF)in rats with chronic heart failure(CHF).Methods: Forty-four Wistar rats were randomly allocated into sham-operation group, model group, Iva group and positive control group(betaloc group).Except the control group,the rats in other 3 groups were used to construct heart failure model by narrowing the abdominal aorta.At the end of the 6th week, the left ventricular end-diastolic pressure(LVEDP)was measured, and LVEDP≥15 mmHg was regarded as modeling-standards.Iva group was fed 10 mg/kg Iva per day and 10 mg/kg betaloc for betaloc group each day. The sham operation group and the blank control group were given normal saline.At the end of the 12th week,LVEDP, the expression of connective tissue growth factor(CTGF)as well as superoxide dismutase(SOD)content in myocardium were also determined.HE and Masson staining were used to detect the degree of myocardial fibrosis.Results: Compared with the sham operation group, the LVEDP of the model group was significantly increased(P<0.01), the content of SOD was significantly decreased(P<0.01)and the expression of CTGF was significantly increased(P<0.01),and the degree of myocardial fibrosis was extremely serious. After treatment with Iva, the content of SOD was significantly increased(P<0.01), however, LVEDP and the expression of CTGF were significantly reduced(P<0.01),and the degree of myocardial fibrosis was obviously alleviated.Conclusion: Iva can significantly reduce the LVEDP of CHF rats, increase the SOD content, inhibit CTGF expression in myocardial tissue, which may have inhibitory effects on myocardial fibrosis in rats with CHF