神经调节蛋白-1β在压力超负荷大鼠肥大心肌组织中的表达下降

Decreased expression of neuregulin-1β in myocardium of hypertrophic rats induced by pressure-overloaded

目的研究NRG-1β在压力超负荷心肌肥大大鼠心肌中的变化。方法复制心肌肥大模型,将模型及假手术动物各随机分成2组:4周模型组(4wM)和8周模型组(8wM组)。采用心动超声及血流动力学评价心功能;Masson染色观察心肌结构;放射免疫法检测心肌中血管紧张素Ⅱ(AngⅡ)含量;Real-time PCR及Westrrn blot检测心肌中神经调节蛋白-1(NRG-1β)mRNA及蛋白的表达。结果 1)和4周对照组(4wC组)比较,4wM组左室射血分数(LVEF)、短轴缩短率(LVFS)、左室收缩末压(LVESP)、左室内压最大上升和下降速率(±dP/dt max)下降(P<0.05),左室收缩末内径(LVEDD)、舒张末内径(LVESD)、左室舒张末压(LVEDP)及心肌胶原容积分数(CVF)增高(P<0.05,P<0.01),心肌中AngⅡ表达增加(P<0.01)。2)和8周模型组(8wC组)比较,8wM组LVEF、LVFS、LVESP、±dP/dt max下降(P<0.01),LVEDD、LVESD、LVEDP及CVF增高(P<0.05,P<0.01),心肌中AngⅡ表达增加,NRG-1βmRNA及蛋白表达下降(P<0.01)。结论 NRG-1β在压力超负荷心肌肥大大鼠心肌中表达下调,可能参与了压力超负荷所致心肌肥大的发生和发展。

Objective To investigate the expression profile of neuregulin-1β（NRG-1β） at mRNA and protein level in myocardium of hypertrophic rats induced by pressure-overloaded. Methods Wistar rats were randomly divided into four groups： myocardial hypertrophy groups （Model） of 4 weeks and 8 weeks, control operation groups （Control） of 4 weeks and 8 weeks. Model groups were operated with abdominal aortic constriction. Hemodynamic and echocardio- grophic characteristics were evaluated ; masson staining was employed to observe the pathological lesions of myocardial tissues; radioimmunological method was used to detect angiotensin Ⅱ （Ang Ⅱ）; expression of NRG-1β mRNA and protein in myocardium were tested by real-time PCR and western blot. Results 1） Compared with 4wC, left ventric- ular ejection fraction （LVEF）, left ventricular fraction shortening （LVFS）, left ventricular end systolic pressure （ LVESP）, Maximal rate of increase in left ventricular pressure （ ± dP/dtmax ） of 4wM were decreased （ P 〈 0. 05 ）, while left ventricular end-systolic diameter （LVEDD） ,left ventricular end-diastolic diameter （LVESD） ,left ventricu-lar end diastolic pressure （LVEDP）, collagen volume fraction （CVF） and Ang Ⅱ of 4wM were increased（P 〈 0. 05, P 〈0. 01 ）,NRG-1β mRNA and protein expression of 4wM group were not exchanged （P 〉 0. 05）. 2）Compared with 8wC, LVEF, LVFS, LVESP,±dP/dtmax of 4wM were decreased （ P 〈 0. 01 ）, LVEDD, LVESD, LVEDP, CVF and Ang Ⅱ were increased（P 〈 0. 05,P 〈 0. 01 ）, NRG-1β mRNA and protein expression of 8wM group were decreased （P 〈0. 01 ）. Conclusions The expression of NRG-1β in myocardium of hypertrophic rats induced by pressure-over- loaded is down-regulated ,which may be involved in the myocardial hypertrophy development.