有氧运动对心力衰竭大鼠循环儿茶酚胺的影响及机制

Effects of Aerobic Exercise on Plasma Catecholamine in Rats with Heart Failure and Its Mechanisms

目的:观察有氧运动对心力衰竭(心衰)大鼠肾上腺G蛋白耦联受体激酶2(GRK2)、α_2-肾上腺素受体(α_2-AR)以及血浆儿茶酚胺含量的影响,探讨运动抑制心衰时交感神经过度激活的可能机制。方法:36只健康雄性Wistar大鼠随机分为假手术安静对照组(SH-sed组)、心衰安静组(HF-sed组)和心衰运动组(HF-ex组)。HF-ex组大鼠进行10周跑台运动,SH-sed组和HF-sed组维持安静水平。实验后利用超声心动图仪检测心脏结构与功能; Masson染色检测心肌胶原容积分数(CVF);高压液相色谱法分析血浆肾上腺素(EP)和去甲肾上腺素(NEP)浓度;实时荧光定量PCR检测心脏重塑基因I型胶原(Col-1)、心钠素(ANF)和转化生长因子-β1(TGF-β1) mRNA表达,western blot检测肾上腺GRK2和α_2-AR蛋白表达水平。结果:1)与SH-sed组比较,HF-sed组缩短分数(FS)和左室射血分数(LVEF)降低(P <0. 05);血浆EP和NEP升高(P <0. 05);心脏Col-1、ANF和TGF-β1 mRNA以及肾上腺GRK2蛋白表达量上调,肾上腺α_2-AR蛋白水平下调(P <0. 05)。2)与HF-sed组比较,HF-ex组FS和LVEF升高(P <0. 05);血浆EP和NEP降低(P <0. 05);心脏Col-1、ANF和TGF-β1 mRNA水平以及肾上腺GRK2蛋白表达下调(P <0. 05),肾上腺α_2-AR蛋白表达上调(P <0. 05)。结论:1)心衰时肾上腺GRK2/α_2-AR信号通路异常造成儿茶酚胺大量分泌,最终引起心脏重塑以及心功能不全。2)长期有氧运动改善心衰大鼠心脏重塑并提高心功能,其机制与肾上腺GRK2/α_2-AR轴功能部分恢复进而抑制儿茶酚胺过度释放有关。

Objective: To observe the effects of aerobic training on adrenal G protein-coupled receptor kinase-2( GRK2),α2-adrenergic receptor( α2-AR) and plasma catecholamine in rats with heart failure and to investigate the possible mechanism of exercise induced inhibition on over activation of sympathetic nervous. Methods: Thirtysix healthy male Wistar rats were randomly divided into sham-operation sedentary group( HF-sed group),heartfailure sedentary control group( HF-sed group) and heart-failure exercise group( HF-ex group). Rats in HF-ex group finished 10-week treadmill training while rats of SH-sed and HF-sed groups kept resting state. After the experiment,cardiac structure and function were detected by ultrechocardiograph;collagen volume fraction( CVF)was tested by Masson staining;plasma epinephrine( EP) and norepinephrine( NEP) were measured by high pressure liquid chromatography;mRNA of cardiac collagen type I( Col-1),atrial natriuretic factor( ANF) and transforming growth factor-β1( TGF-β1) were tested by real-time quantitative PCR and the protein level of adrenal GRK2 and α2-AR was explored by Western blotting. Results: 1) Compared with SH-sed group,fractional shortening( FS) and left ventricular ejection fraction( LVEF) in HF-sed group decreased( P < 0. 05),plasma EP and NEP increased( P < 0. 05),mRNA expression of heart Col-1,ANF and TGF-β1( remodeling genes),and protein of adrenal GRK2 were upregulated( P < 0. 05) while adrenal α2-AR protein was downregulated( P < 0. 05) in HF-sed group. 2) Compared with HF-sed group,FS and LVEF in HF-ex group increased( P < 0. 05),plasma EP and NEP decreased( P < 0. 05),mRNA expression of Col-1,ANF and TGF-β1,and protein expression of adrenal GRK2 were downregulated( P < 0. 05) while adrenal α2-AR protein was unregulated( P < 0. 05) in HF-ex group. Conclusion: 1) Abnormal GRK2/α2-AR signaling pathway in the adrenal gland during heart failure results in a large amount of catecholamine secretion,which eventually leads to cardiac remodeling and cardiac dysfunction. 2) Long-term aerobic exercise improves cardiac remodeling and improves cardiac function in rats with heart failure. The mechanism is related to the partial recovery of adrenal GRK2/α2-AR axis function and the inhibition of excessive release of catecholamine.