An Steven S, Fredberg Jeffrey J
Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, Room E-7616, Baltimore, MD 21205, USA.
Can J Physiol Pharmacol. 2007 Jul;85(7):700-14. doi: 10.1139/Y07-059.
Airway hyperresponsiveness is the excessive narrowing of the airway lumen caused by stimuli that would cause little or no narrowing in the normal individual. It is one of the cardinal features of asthma, but its mechanisms remain unexplained. In asthma, the key end-effector of acute airway narrowing is contraction of the airway smooth muscle cell that is driven by myosin motors exerting their mechanical effects within an integrated cytoskeletal scaffolding. In just the past few years, however, our understanding of the rules that govern muscle biophysics has dramatically changed, as has their classical relationship to airway mechanics. It has become well established, for example, that muscle length is equilibrated dynamically rather than statically, and that in a dynamic setting nonclassical features of muscle biophysics come to the forefront, including unanticipated interactions between the muscle and its time-varying load, as well as the ability of the muscle cell to adapt (remodel) its internal microstructure rapidly in response to its ever-changing mechanical environment. Here, we consider some of these emerging concepts and, in particular, focus on structural remodeling of the airway smooth muscle cell as it relates to excessive airway narrowing in asthma.
气道高反应性是指在正常个体中几乎不会或完全不会引起气道狭窄的刺激因素，却能导致气道管腔过度狭窄。它是哮喘的主要特征之一，但其发病机制仍不清楚。在哮喘中，急性气道狭窄的关键终效应器是气道平滑肌细胞的收缩，这是由肌球蛋白马达在整合的细胞骨架支架内发挥机械作用驱动的。然而，就在过去几年里，我们对肌肉生物物理学规律的理解发生了巨大变化，它们与气道力学的经典关系也是如此。例如，已经明确肌肉长度是动态平衡而非静态平衡，并且在动态环境中，肌肉生物物理学的非经典特征变得更加突出，包括肌肉与其随时间变化的负荷之间意想不到的相互作用，以及肌肉细胞响应不断变化的机械环境而快速调整（重塑）其内部微观结构的能力。在此，我们探讨其中一些新出现的概念，尤其关注气道平滑肌细胞的结构重塑与哮喘中气道过度狭窄的关系。
