神经调节蛋白-1对糖尿病心肌病大鼠心肌重构的影响

目的观察神经调节蛋白-1(NRG-1)对糖尿病心肌病大鼠心肌重构的影响并初步探讨其机制。方法♂SD大鼠经腹腔注射链脲佐菌素诱导糖尿病心肌病(DCM)模型,对照组(Control)大鼠给予腹腔注射PBS溶液。成模后12周大鼠分为DCM组(隔日1次尾静脉注射PBS液)、NRG-1组(隔日1次尾经脉注射重组NRG-1)、HERCE组(隔日1次尾经脉注射重组NRG-1及Herceptin),药物干预共2周,观察2周于DCM造模后16周,采用心脏超声评估糖尿病心肌病大鼠心功能变化;原位末端标记法(TUNEL)检测心肌细胞凋亡,Masson特殊胶原染色定量检测心肌胶原纤维,实时定量RT-PCR法检测心肌组织相关基因表达情况。结果糖尿病诱导16周后,DCM组大鼠心功能降低,表现为左室射血分数(LVEF)、左室短轴缩短率(FS)、舒张早期运动速度/舒张晚期运动速度(Em/Am)较对照组下降(P<0.05)。凋亡指数(AI)、胶原容积分数(CVF)、Ⅰ/Ⅲ型胶原mRNA表达上调,bcl-2 mRNA下调而bax mRNA上调(P<0.05)。与DCM组相比,NRG-1组LVEF、FS、bcl-2 mRNA上调(P<0.05),AI、CVF、Ⅰ/Ⅲ型胶原mRNA、bax mRNA表达下调(P<0.05)。与NRG-1组比较,HERCE组以上各指标变化无统计学意义(P>0.05)。结论外源性补给NRG-1可抑制心肌细胞的凋亡、减轻心肌纤维化,从而改善DCM大鼠心功能。

Effects of neuregulin-1 on ventricular remolding in experimental diabetic cardiomyopathy

Aim To investigate the effect of neuregulin-1 on ventricular remolding in rats with diabetic cardiomyopathy and the signaling mechanism.Methods Diabetes was induced by intraperitoneal injection of streptozotocin in male SD rats and the control group rats were injected i.p.with PBS at the same time.12 weeks after injection,diabetic rats were randomly divided into DCM group,NRG-1 group(0.01μg·g-1 rNRG-1 injected by tail vein every 2 days during the next 2 weeks) and HERCE group(rNRG-1 0.01 μg·g-1 and Herceptin 0.01 μg·g-1 injected by tail vein every 2 days during the next 2 weeks).After intervened for another 2 weeks(16 weeks after induction of diabetes),heart function of the experimental rats was detected by echocardiography,apoptosis of cardiomyocytes was measured by Tunel staining,myocardial collagen contents was quantified by Masson staining and the related gene expressions were analyzed by quantitative real-time PCR.Results By the end of the experiment,the LVEF,FS and Em/Am in the DCM group were lower than those in the control group(P<0.05),the apoptotic index(AI),collagen volume fraction(CVF) and the mRNA of type Ⅰ and type Ⅲ collagen levels were higher than those in the control group(P<0.05).Apoptosis related mRNA of bcl-2 was lower and bax was higher in the DCM group than in the control group(P<0.05).Compared with the DCM group,the LVEF,FS,Em/Am and mRNA of bcl-2 were increased and the AI,CVF and the mRNA of type Ⅰ,type Ⅲ collagen and mRNA of bax levels were decreased in NRG-1 group(P<0.05).However,the parameters mentioned above had no difference between the DCM group and the HERCE group(P>0.05).Conclusion Exogenous supply of NRG-1 can improve cardiac function and reverse remodeling of the heart of DCM rats by regulating cardiomyocyte apoptosis and cardiac fibrosis.