有氧运动调控神经生长因子表达改善心力衰竭大鼠心脏交感神经功能

Aerobic Exerise Training Improves the Cardiac Sympathetic Nerve Function through Regulating the Nerve Growth Factor Expression in Heart Failure Rats

目的:观察有氧运动对心力衰竭(心衰)大鼠心脏重塑以及心脏交感神经功能的影响并探讨神经生长因子(NGF)及其受体(TrkA)在其间的作用机制。方法:36只Wistar大鼠随机分为假手术对照组(Sham组)、心衰安静组(HF-sed组)和心衰运动组(HF-ex组),每组12只。HF-sed组和HF-ex组通过结扎冠状动脉前降支建立心肌梗塞后心衰模型,Sham组开胸后分离左冠状动脉前降支但不结扎。随后HF-ex组进行10周跑台运动,Sham组和HF-sed组于鼠笼内安静饲养。实验后利用超声心动术检测心脏结构与功能,Masson染色法观察组织病理学变化并计算心肌胶原容积分数(CVF);高压液相色谱法测定心肌和血浆去甲肾上腺素(NE)含量;分别利用实时荧光定量PCR和Western blot技术检测心肌NGF、TrkA、去甲肾上腺素转运体(NET)和酪氨酸羟化酶(TH)mRNA和蛋白表达水平。结果:(1)与Sham组比较,HF-sed组大鼠发生左室肥大、心肌纤维化(CVF升高)、心功能下降;血浆NE含量升高,心肌NE含量降低;心肌NGF、TrkA和TH mRNA与蛋白以及NET蛋白表达量降低(P<0.05)。(2)与HF-sed组比较,HF-ex组左室肥大以及心肌纤维化减轻,心功能提高;血浆NE含量降低(P<0.05),心肌NE含量升高(P<0.05);心肌NGF、TrkA和TH mRNA与蛋白以及NET蛋白表达量升高(P<0.05)。结论:长期有氧运动通过改善心衰大鼠心脏交感神经功能逆转心脏重塑并提高心功能,其机制可能与NGF与TrkA表达上调进而部分恢复NET功能有关。

Objective To observe the effect of aerobic exercises on cardiac remodeling and cardiac sympathetic nerve function in rats with heart failure and investigate the possible mechanism of nerve growth factor(NGF)and its receptor(TrkA).Methods Thirty-six Wistar rats were randomly divided into a sham operation control(Sham),a heart failure sedentary(HF-sed)and a heart failure exercise(HF-ex)groups with 12 animals in each group.The heart failure model of the post myocardial infarction was stimulated by ligating the anterior descending branch of the coronary artery in HF-sed and HF-ex groups,while in the Sham group the anterior descending branch of the coronary artery was separated without ligating after thoracotomy.Then rats in HF-ex group conducted 10-week treadmill exercise training and those of Sham and HF-sed groups were quietly in cage.Then,the cardiac structure and function were measured using the ultrechocardiography.Masson staining was used to observe the histopathologic changes and the collagen volume fraction(CVF)was calculated.The myocardial and plasma norepinephrine(NE)were measured using the high-pressure liquid chromatography,and the gene expression(mRNA and protein)level of myocardial NGF,TrkA,norepinephrine transporter(NET)and tyrosine hydroxylase(TH)were detected using the real-time fluorescent quantitation polymerase chain reaction and Western blotting.Results Compared with Sham group,the left ventricular hypertrophy,myocardial fibrosis(CVF increased),increased plasma NE content and reduced cardiac function,mRNA and protein expression level of myocardial NGF,TrkA and TH as well as NET protein were observed in HF-sed group(P<0.05).Compared with HF-sed group,the left ventricular hypertrophy and myocardial fibrosis alleviated,cardiac function increased,plasma NE content reduced but myocardial NE increased(P<0.05),as well as mRNA and protein expression level of myocardial NGF,TrkA and TH,and NET protein upregulated in HF-ex group(P<0.05).Conclusion The long-term aerobic exercise training reverses cardiac remodeling and enhances cardiac function via the improvement of cardiac sympathetic nerve function in rats of heart failure,whose mechanism may be related to the upregulation of NGF and TrkA gene expression and partly restored NET function.