重组人纽兰格林对心力衰竭大鼠线粒体功能的影响

目的观察重组人纽兰格林(neuregulin,NRG)对心力衰竭(HF)大鼠线粒体功能的影响,并探讨其机制。方法雄性Wister大鼠40只,结扎大鼠左冠状动脉建立缺血性HF模型。4周后,建模成功的24只大鼠随机分为NRG组NRG 10μg/(kg·d)],AG825组AG825 50μg/(kg·d)]及HF组,各组8只,另6只大鼠作为假手术组(Sham组)。各组干预10 d,于实验结束时提取左心室梗死区外心肌线粒体,测定线粒体膜电位(MMP)、呼吸控制率(RCR)及组织ATP酶活性,同时测定活性氧水平及谷胱甘肽过氧化物酶(GSHPX)mRNA水平。结果与Sham组比较,HF组大鼠线粒体功能受损,MMP下降、RCR及ATP酶活性降低,活性氧生成增加,GSHPX mRNA表达减少。与HF组比较,NRG组大鼠MMP增高,线粒体RCR改善,ATP酶活性增多,活性氧生成减少,GSHPXmRNA表达增加,而AG825组RCR、MMP和ATP酶活性均明显降低(P<0.05,P<0.01)。结论 NRG明显改善衰竭大鼠线粒体功能,NRG对衰竭心肌线粒体功能的保护作用,可能与其抗氧化应激作用有关。

Effect of recombinant human neuregulin on mitochondrial function in heart failure rats

Objective To study the effect of recombinant human neuregulin(NRG) on mitochondrial function in heart failure(HF) rats.Methods Forty-six adult Wister rats were included in this study.Four weeks after a rat ischemic HF model was established by ligation of the left coronary artery,the surviving 24 rats were randomized into NRG group(10μg/kg ? d),AG825 group(50μg/kg ? d) and HF group(8 in each group).Another 6 rats served as a sham operation group. Then,mitochondrial samples were taken from the left ventriclular infarction area.Mitochondrial membrane potential(MMP),respiration control rate(RCR),ATP activity,activated oxygen and glutathione peroxidase(GSHPX) mRNA expression level were measured.Results The impairment of mitochondria was severer and the MMP,RCR,ATP activity were lower while the production of activated oxygen was higher and the GSHPX mRNA expresion level was lower in HF group than in sham operation group.The MMP,RCR and ATP activity were higher while the production of activated oxygen was lower and the GSHPX mRNA expresion level was higher in NRG group than in HF group.The MMP,RCR and ATP activity were significantly lower in AG825 group than in NRG and HF groups(P<0.05,P<0.01).Conclusion NRG can significantly improve the mitochondrial function in HF rats,which may be related to its anti-oxidative effect.