Kalotas Jack O, Wang Carolyn J, Noble Peter B, Wang Kimberley C W
School of Human Sciences, The University of Western Australia, Crawley, WA, Australia.
Telethon Kids Institute, The University of Western Australia, Nedlands, WA, Australia.
Front Med (Lausanne). 2021 May 31;8:674324. doi: 10.3389/fmed.2021.674324. eCollection 2021.
Intrauterine growth restriction (IUGR) is associated with asthma. Murine models of IUGR have altered airway responsiveness in the absence of any inflammatory exposure. Given that a primary feature of asthma is airway inflammation, IUGR-affected individuals may develop more substantial respiratory impairment if subsequently exposed to an allergen. This study used a maternal hypoxia-induced mouse model of IUGR to determine the combined effects of IUGR and allergy on airway responsiveness. Pregnant BALB/c mice were housed under hypoxic conditions (10.5% O) from gestational day (GD) 11-GD 17.5 (IUGR group; term = GD 21). Following hypoxic exposure, mice were returned to a normoxic environment (21% O). A second group of pregnant mice were housed under normoxic conditions throughout pregnancy (Control). All offspring were sensitized to ovalbumin (OVA) and assigned to one of four treatment groups: Control - normoxic and saline challenge; IUGR - hypoxic and saline challenge; Allergy - normoxic and OVA challenge; and IUGR + Allergy - hypoxic and OVA challenge. At 8 weeks of age, and 24 h post-aerosol challenge, mice were tracheostomised for methacholine challenge and assessment of lung mechanics by the forced oscillation technique, and lungs subsequently fixed for morphometry. IUGR offspring were lighter than Control at birth and in adulthood. Both Allergy and IUGR independently increased airway resistance after methacholine challenge. The IUGR group also exhibited an exaggerated increase in tissue damping and elastance after methacholine challenge compared with Control. However, there was no incremental effect on airway responsiveness in the combined IUGR + Allergy group. There was no impact of IUGR or Allergy on airway structure and no effect of sex on any outcome. IUGR and aeroallergen independently increased bronchoconstrictor response, but when combined the pathophysiology was not worsened. Findings suggest that an association between IUGR and asthma is mediated by baseline airway responsiveness rather than susceptibility to allergen.
宫内生长受限（IUGR）与哮喘有关。在没有任何炎症暴露的情况下，IUGR小鼠模型的气道反应性发生了改变。鉴于哮喘的一个主要特征是气道炎症，IUGR影响的个体如果随后接触过敏原，可能会出现更严重的呼吸功能损害。本研究使用母体缺氧诱导的IUGR小鼠模型来确定IUGR和过敏对气道反应性的联合影响。怀孕的BALB/c小鼠在妊娠第11天至第17.5天（IUGR组；足月为妊娠第21天）置于缺氧条件（10.5%氧气）下饲养。缺氧暴露后，小鼠返回常氧环境（21%氧气）。第二组怀孕小鼠在整个孕期置于常氧条件下（对照组）。所有后代均对卵清蛋白（OVA）致敏，并分为四个治疗组之一：对照组 - 常氧和盐水激发；IUGR组 - 缺氧和盐水激发；过敏组 - 常氧和OVA激发；IUGR + 过敏组 - 缺氧和OVA激发。在8周龄时，雾化激发后24小时，对小鼠进行气管切开术以进行乙酰甲胆碱激发，并通过强迫振荡技术评估肺力学，随后将肺固定以进行形态学测量。IUGR后代在出生时和成年期比对照组轻。过敏组和IUGR组在乙酰甲胆碱激发后均独立增加气道阻力。与对照组相比，IUGR组在乙酰甲胆碱激发后组织阻尼和弹性也有过度增加。然而，IUGR + 过敏联合组对气道反应性没有增量影响。IUGR或过敏对气道结构没有影响，性别对任何结果也没有影响。IUGR和气源性过敏原独立增加支气管收缩反应，但联合时病理生理学并未恶化。研究结果表明，IUGR与哮喘之间的关联是由基线气道反应性介导的，而不是对过敏原的易感性。
