The effects of repeated allergen challenge on airway smooth muscle structural and molecular remodeling in a rat model of allergic asthma
The effects of repeated allergen challenge on airway smooth muscle structural and molecular remodeling in a rat model of allergic asthma
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DOI：
10.1152/ajplung.00142.2009
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发表时间：
2009-10-01
影响因子：
4.9
通讯作者：
Martin, James G.
中科院分区：
文献类型：
--
作者：
Labonte, Isabelle;Hassan, Muhannad;Martin, James G.
拉邦特I，哈桑·M，瑞斯·PA，图西娅·K，拉维奥莱特·M，劳松·AM，马丁·J·G。过敏原反复激发对过敏性哮喘大鼠气道平滑肌结构和分子重塑的影响。AM J Physiol肺细胞分子Physiol 297：L698-L705,2009。2009年7月31日首次出版；DOI：10.1152/ajpeng.00142.2009。-在活体内，关于增生引起的气道平滑肌(SM)重塑对气道SM收缩性能的影响的研究很少。本研究的目的是探讨变应原诱导的气道SM增生与其收缩表型的关系。在第0天用卵白蛋白(OVA)或生理盐水致敏棕色挪威大鼠，然后在第14天1次OVA攻击后24小时处死，或OVA攻击3次(第14、19和24天)后2天或7天后处死。观察肌球蛋白总质量、肌球蛋白重链快速亚型(SM-B)和肌球蛋白轻链激酶(MLCK)的表达、体外气管收缩和体内对乙酰胆碱(MCH)的气道反应性的变化。OVA单次激发后1天，增殖细胞核抗原阳性的SM细胞数量明显多于对照组，而SM质量、收缩表型和气管收缩能力无明显变化。3次攻击后第2天，SM质量和增殖细胞核抗原免疫反应细胞数分别增加3倍和10倍(P<；0.05)，但气道对MCH的反应性未受影响。SM质量归一化后，总肌球蛋白、SM-B和MLCK在mRNA水平表达降低(P<；0.05)，总肌球蛋白和MLCK在蛋白水平表达降低(P<；0.05)。反复激发2天后，归一化气管SM力的产生也显著降低(P<；0.05)。在反复挑战7天后，重塑特征恢复到对照水平。变应原诱导的SM细胞的增殖与收缩表型的丧失有关，这被质量的增加所抵消。
Labonte I, Hassan M, Risse PA, Tsuchiya K, Laviolette M, Lauzon AM, Martin JG. The effects of repeated allergen challenge on airway smooth muscle structural and molecular remodeling in a rat model of allergic asthma. Am J Physiol Lung Cell Mol Physiol 297: L698-L705, 2009. First published July 31, 2009; doi:10.1152/ajplung.00142.2009.-The effects of remodeling of airway smooth muscle (SM) by hyperplasia on airway SM contractility in vivo are poorly explored. The aim of this study was to investigate the relationship between allergen-induced airway SM hyperplasia and its contractile phenotype. Brown Norway rats were sensitized with ovalbumin ( OVA) or saline on day 0 and then either OVA-challenged once on day 14 and killed 24 h later or OVA-challenged 3 times ( on days 14, 19, and 24) and killed 2 or 7 days later. Changes in SM mass, expression of total myosin, SM myosin heavy chain fast isoform (SM-B) and myosin light chain kinase (MLCK), tracheal contractions ex vivo, and airway responsiveness to methacholine (MCh) in vivo were assessed. One day after a single OVA challenge, the number of SM cells positive for PCNA was greater than for control animals, whereas the SM mass, contractile phenotype, and tracheal contractility were unchanged. Two days after three challenges, SM mass and PCNA immunoreactive cells were increased (3- and 10-fold, respectively; P < 0.05), but airway responsiveness to MCh was unaffected. Lower expression in total myosin, SM-B, and MLCK was observed at the mRNA level ( P < 0.05), and total myosin and MLCK expression were lower at the protein level ( P < 0.05) after normalization for SM mass. Normalized tracheal SM force generation was also significantly lower 2 days after repeated challenges ( P < 0.05). Seven days after repeated challenges, features of remodeling were restored toward control levels. Allergen-induced hyperplasia of SM cells was associated with a loss of contractile phenotype, which was offset by the increase in mass.