Fredberg J J, Inouye D S, Mijailovich S M, Butler J P
Physiology Program, Harvard School of Public Health, Boston, Massachusetts, USA.
Am J Respir Crit Care Med. 1999 Mar;159(3):959-67. doi: 10.1164/ajrccm.159.3.9804060.
In asthma, the mechanisms relating airway obstruction, hyperresponsiveness, and inflammation remain rather mysterious. We show here that regulation of airway smooth muscle length corresponds to a dynamically equilibrated steady state, not the static mechanical equilibrium that had been previously assumed. This dynamic steady state requires as an essential feature a continuous supply of external mechanical energy (derived from tidal lung inflations) that acts to perturb the interactions of myosin with actin, drive the molecular state of the system far away from thermodynamic equilibrium, and bias the muscle toward lengthening. This mechanism leads naturally to the suggestion that excessive airway narrowing in asthma may be associated with the destabilization of that dynamic process and its resulting collapse back to static equilibrium. With this collapse the muscle undergoes a phase transition and virtually freezes at its static equilibrium length. This mechanism may help to elucidate several unexplained phenomena including the multifactorial origins of airway hyperresponsiveness, how allergen sensitization leads to airway hyperresponsiveness, how hyperresponsiveness can persist long after airway inflammation is resolved, and the inability in asthma of deep inspirations to relax airway smooth muscle.
在哮喘中，气道阻塞、高反应性和炎症之间的机制仍然相当神秘。我们在此表明，气道平滑肌长度的调节对应于一种动态平衡的稳态，而非先前假定的静态力学平衡。这种动态稳态的一个基本特征是需要持续供应外部机械能（源自肺的潮气量充气），该能量作用于扰乱肌球蛋白与肌动蛋白的相互作用，驱使系统的分子状态远离热力学平衡，并使肌肉倾向于延长。这一机制自然地引出这样的推测：哮喘中气道过度狭窄可能与该动态过程的不稳定及其导致的恢复到静态平衡有关。随着这种恢复，肌肉经历相变并实际上在其静态平衡长度处冻结。这一机制可能有助于阐明一些无法解释的现象，包括气道高反应性的多因素起源、变应原致敏如何导致气道高反应性、气道炎症消退后高反应性如何能长期持续，以及哮喘患者深吸气时无法舒张气道平滑肌的现象。
