反复中等强度有氧训练能降低哮喘小鼠的气道反应性
2009/07/10
我们在卵清蛋白（OVA）致敏的小鼠模型中发现，中等强度有氧训练能降低气道炎症。本实验研究反复中等强度训练对该模型小鼠气道高反应性（AHR）的影响。
小鼠采用OVA致敏或注射生理盐水作为对照，对其进行中等强度的训练，每周3次，连续4周。训练结束后，通过机械通气检测小鼠AHR。
结果显示，与对照组小鼠相比，训练能降低OVA 致敏小鼠60％的肺阻力，此外还能减少气道平滑肌（ASM）的厚度。与之相反，训练能使两组小鼠循环肾上腺素提高3倍。由于肾上腺素结合β2肾上腺受体（AR），促进支气管扩张。因此我们研究了β2-AR在训练介导的AHR改善中的作用。在卵清蛋白致敏小鼠中，我们采用β2-AR拮抗剂盐酸丁氧胺阻断训练对肺阻力的影响，同时在ASM细胞中检测β2-AR和G蛋白受体激酶-2（GRK-2）的表达变化。GRK-2能促进β2-AR脱敏。OVA致敏小鼠中，训练对ASM细胞β2-AR表达无影响，然而与对照组相比，训练能降低50％的GRK-2表达。此外，训练能使OVA致敏小鼠前列腺素E2（PGE2）的产生降低5倍，但对肺内E类前列腺素-1（EP-1）受体的表达无影响。PGE2和EP-1均参与了β2-AR的脱敏作用。
综上所述，本研究显示，中等强度有氧训练能可能通过调节β2-AR，降低气道高反应性。
（苏楠 审校）
Am J Respir Cell Mol Biol. 2009 May 7. [Epub ahead of print]
Repeated Bouts of Moderate Intensity Aerobic Exercise Reduce Airway Reactivity in a Murine Asthma Model.
Hewitt M, Estell K, Davis IC, Schwiebert LM.
We have reported that moderate intensity aerobic exercise training attenuates airway inflammation in mice sensitized/challenged with ovalbumin (OVA). The current study determined the effects of repeated bouts of aerobic exercise at a moderate intensity on airway hyperresponsiveness (AHR) in these mice. Mice were sensitized/challenged with OVA or saline and exercised at a moderate intensity 3X / wk for 4 wks. At protocol completion, mice were analyzed for changes in AHR via mechanical ventilation. Results show that exercise decreased total lung resistance 60% in OVA-treated mice as compared with controls; exercise also decreased airway smooth muscle (ASM) thickness. In contrast, exercise increased circulating epinephrine levels 3-fold in saline- and OVA-treated mice. Because epinephrine binds beta2-adrenergic receptors (AR), which facilitate bronchodilatation, the role of beta2-AR in exercise-mediated improvements in AHR was examined. Application of the beta2-AR antagonist butoxamine HCl blocked the effects of exercise on lung resistance in OVA-treated mice. In parallel, ASM cells were examined for changes in the protein expression of beta2-AR and G-protein receptor kinase-2 (GRK-2); GRK-2 promotes beta2-AR desensitization. Exercise had no effect beta2-AR expression in ASM cells of OVA-treated mice; however, exercise decreased GRK-2 expression by 50% as compared with controls. Exercise also decreased prostaglandin E2 (PGE2) production 5-fold but had no affect on E prostanoid-1 (EP1) receptor expression within the lungs of OVA-treated mice; both PGE2 and the EP1 receptor have been implicated in beta2-AR desensitization. Together, these data indicate that moderate intensity aerobic exercise training attenuates AHR via a mechanism that involves beta2-AR.
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