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一种用于研究气道平滑肌对机械振荡适应性的成熟模型。

A maturational model for the study of airway smooth muscle adaptation to mechanical oscillation.

作者信息

Wang Lu, Chitano Pasquale, Murphy Thomas M

机构信息

Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, USA.

出版信息

Can J Physiol Pharmacol. 2005 Oct;83(10):817-24. doi: 10.1139/y05-057.

Abstract

It has been shown that mechanical stretches imposed on airway smooth muscle (ASM) by deep inspiration reduce the subsequent contractile response of the ASM. This passive maneuver of lengthening and retraction of the muscle is beneficial in normal subjects to counteract bronchospasm. However, it is detrimental to hyperresponsive airways because it triggers further bronchoconstriction. Although the exact mechanisms for this contrary response by normal and hyperresponsive airways are unclear, it has been suggested that the phenomenon is related to changes in ASM adaptability to mechanical oscillation. Healthy immature airways of both human and animal exhibit hyperresponsiveness, but whether the adaptative properties of hyperresponsive airway differ from normal is still unknown. In this article, we review the phenomenon of ASM adaptation to mechanical oscillation and its relevance and implication to airway hyperresponsiveness. We demonstrate that the age-specific expression of ASM adaptation is prominent using an established maturational animal model developed in our laboratory. Our data on immature ASM showed potentiated contractile force shortly after a length oscillation compared with the maximum force generated before oscillation. Several potential mechanisms such as myogenic response, changes in actin polymerization, or changes in the quantity of the cytoskeletal regulatory proteins plectin and vimentin, which may underlie this age-specific force potentiation, are discussed. We suggest a working model of the structure of smooth muscle associated with force transmission, which may help to elucidate the mechanisms responsible for the age-specific expression of smooth muscle adaptation. It is important to study the maturational profile of ASM adaptation as it could contribute to juvenile hyperresponsiveness.

摘要

研究表明,深吸气对气道平滑肌(ASM)施加的机械牵张会降低随后ASM的收缩反应。这种肌肉的被动拉长和回缩操作对正常受试者有益,可对抗支气管痉挛。然而,它对高反应性气道是有害的,因为它会引发进一步的支气管收缩。尽管正常气道和高反应性气道这种相反反应的确切机制尚不清楚,但有人认为该现象与ASM对机械振荡适应性的变化有关。人和动物健康的未成熟气道均表现出高反应性,但高反应性气道的适应性特性是否与正常气道不同仍不清楚。在本文中,我们综述了ASM对机械振荡的适应性现象及其与气道高反应性的相关性和意义。我们使用在我们实验室建立的成熟动物模型证明,ASM适应性的年龄特异性表达很突出。我们关于未成熟ASM的数据显示,与振荡前产生的最大力相比,长度振荡后不久收缩力增强。讨论了几种可能是这种年龄特异性力增强基础的潜在机制,如肌源性反应、肌动蛋白聚合变化或细胞骨架调节蛋白网蛋白和波形蛋白数量的变化。我们提出了一个与力传递相关的平滑肌结构工作模型,这可能有助于阐明负责平滑肌适应性年龄特异性表达的机制。研究ASM适应性的成熟概况很重要,因为它可能导致青少年高反应性。

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