Gil Fulvio R, Lauzon Anne-Marie
Meakins-Christie Laboratories, McGill University, 3626 St-Urbain Street, Montréal, QC H2X 2P2, Canada.
Can J Physiol Pharmacol. 2007 Jan;85(1):133-40. doi: 10.1139/y06-096.
Asthma is a respiratory disorder characterized by airway inflammation and hyperresponsiveness associated with reversible airway obstruction. The relative contributions of airway hyperresponsiveness and inflammation are still debated, but ultimately, airway narrowing mediated by airway smooth muscle contraction is the final pathway to asthma. Considerable effort has been devoted towards identifying the factors that lead to the airway smooth muscle hypercontractility observed in asthma, and this will be the focus of this review. Airway remodeling has been observed in severe and fatal asthma. However, it is unclear whether remodeling plays a protective role or worsens airway responsiveness. Smooth muscle plasticity is a mechanism likely implicated in asthma, whereby contractile filament rearrangements lead to maximal force production, independent of muscle length. Increased smooth muscle rate of shortening via altered signaling pathways or altered contractile protein expression has been demonstrated in asthma and in numerous models of airway hyperresponsiveness. Increased rate of shortening is implicated in counteracting the relaxing effect of tidal breathing and deep inspirations, thereby creating a contracted airway smooth muscle steady-state. Further studies are therefore required to understand the numerous mechanisms leading to the airway hyperresponsiveness observed in asthma as well as their multiple interactions.
哮喘是一种以气道炎症和高反应性为特征的呼吸系统疾病，伴有可逆性气道阻塞。气道高反应性和炎症的相对作用仍存在争议，但最终，由气道平滑肌收缩介导的气道狭窄是哮喘的最终途径。人们已投入大量精力来确定导致哮喘中观察到的气道平滑肌过度收缩的因素，这将是本综述的重点。在重度和致死性哮喘中已观察到气道重塑。然而，尚不清楚重塑是起保护作用还是会加重气道反应性。平滑肌可塑性是一种可能与哮喘有关的机制，通过这种机制，收缩细丝重排可导致最大力量产生，而与肌肉长度无关。在哮喘和众多气道高反应性模型中，已证实通过改变信号通路或改变收缩蛋白表达可提高平滑肌缩短速率。缩短速率增加与抵消潮式呼吸和深呼吸的舒张作用有关，从而形成收缩的气道平滑肌稳态。因此，需要进一步研究以了解导致哮喘中观察到的气道高反应性的众多机制及其多种相互作用。
