Peripheral Airway Smooth Muscle, but Not the Trachealis, Is Hypercontractile in an Equine Model of Asthma.

Peripheral Airway Smooth Muscle, but Not the Trachealis, Is Hypercontractile in an Equine Model of Asthma.
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在马哮喘模型中,周围气道平滑肌(而非气管肌)收缩过度。

DOI:
10.1165/rcmb.2015-0180oc
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发表时间:
2016
影响因子:
6.4
通讯作者:
Lauzon,Anne-Marie
Lauzon,Anne-Marie
中科院分区:
医学1区
文献类型:
--
作者:
Matusovsky,OlegS;Kachmar,Linda;Ijpma,Gijs;Bates,Genevieve;Zitouni,Nedjma;Benedetti,Andrea;Lavoie,Jean-Pierre;Lauzon,Anne-Marie

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Heaves是一种自然发生的马疾病,与人类哮喘有许多相似之处,包括可逆性抗原诱导的支气管收缩、气道炎症和重塑。本研究的目的是确定在马哮喘模型中气管肌是否具有周围气道平滑肌(ASM)的机械代表性。在病情加重或临床缓解的马匹和对照马的气管和周围ASM被解剖并释放上皮,以测量卸载缩短速度(Vmax)、应力(力/横截面积)、获得最大反应50%时的甲胆碱有效浓度和刚度。还测量了肌纤维Mg2+- atp酶活性、肌动球蛋白微动性和收缩蛋白表达。腹胀马的外周气道vmax和Mg2+- atp酶活性显著升高,而气管平滑肌的Mg2+- atp酶活性显著升高。此外,研究还发现vmax与马腹胀后外周气道皮质类固醇治疗结束后的时间之间存在显著相关性。与对照组和恶化马相比,缓解马的周围气道的最大应力和刚度更大,可能是由于重塑。肌动球蛋白的动态活力在对照组和有腹胀的马之间没有差异。这些数据表明,隆起时外周ASM发生机械和生化变化,而气管的行为与对照马相同。因此可以想象气管肌可能也不是人类哮喘外周ASM的代表,但这需要进一步的研究。
Heaves is a naturally occurring equine disease that shares many similarities with human asthma, including reversible antigen-induced bronchoconstriction, airway inflammation, and remodeling. The purpose of this study was to determine whether the trachealis muscle is mechanically representative of the peripheral airway smooth muscle (ASM) in an equine model of asthma. Tracheal and peripheral ASM of heaves-affected horses under exacerbation, or under clinical remission of the disease, and control horses were dissected and freed of epithelium to measure unloaded shortening velocity (Vmax), stress (force/cross-sectional area), methacholine effective concentration at which 50% of the maximum response is obtained, and stiffness. Myofibrillar Mg2+-ATPase activity, actomyosinin vitromotility, and contractile protein expression were also measured. Horses with heaves had significantly greaterVmaxand Mg2+-ATPase activity in peripheral airway but not in tracheal smooth muscle. In addition, a significant correlation was found betweenVmaxand the time elapsed since the end of the corticosteroid treatment for the peripheral airways in horses with heaves. Maximal stress and stiffness were greater in the peripheral airways of the horses under remission compared with controls and the horses under exacerbation, potentially due to remodeling. Actomyosinin vitromotility was not different between controls and horses with heaves. These data demonstrate that peripheral ASM is mechanically and biochemically altered in heaves, whereas the trachealis behaves as in control horses. It is therefore conceivable that the trachealis muscle may not be representative of the peripheral ASM in human asthma either, but this will require further investigation.
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