A study on the airway remodeling in an asthma model using bikunin knock out mice.

【目的】透明质酸可能通过影响气道粘液生成和纤毛搏动与哮喘发病有关。为了直接证明这一假设，我们使用bikunin敲除（BXO）小鼠研究了气道反应性，这是血清源性透明质酸南相关蛋白（SHAP）转移反应所必需的。【方法】制备DBA1或BALBC两种BXO小鼠。我们分别在第1天和第15天给小鼠腹腔注射卵清蛋白（OVA）与盐酸铝混合致敏。通过吸入1% OVA溶液进行气道致敏，从第23天至36天持续2周，或从第23天至50天持续4周。分别在第22天或第37天、第26天或第37天用体容积描记仪（Buxco）测量非特异性气道对甲胆碱的反应和ova特异性气道反应。【结果】吸入OVA致敏后3天、10天，野生小鼠和BXO小鼠对OVA的即时气道反应无显著差异。吸入甲胆碱的非特异性气道反应也得到了类似的结果。两株血清ova特异性IgE和IgG水平及支气管肺泡灌洗结果无显著差异。即使在致敏4周的小鼠中，两种菌株的气道反应也没有显著差异；然而，BXO小鼠血清中ova特异性IgG水平显著升高。【讨论】在目前的研究中，我们未能发现气道反应的明显差异。我们也应该通过测量气管内压力来评估气道反应，而不是通过体表容积描记术。我们还应证实HA或SHAP含量的改变是气道病理改变的先决条件。

【Aims】 It is possible that hyarulonan is related to the pathogenesis of asthma by affecting mucus production and ciliary beat in airways. In order to directly prove this hypothesis, we investigated airway responsiveness using bikunin knock out (BXO) mice, which is essential for the transfer reaction of serum-derived hyarulonan associated protein (SHAP).【Methods】 We made BXO mice form DBA1 or BALBC strain. We sensitized mice with intraperitoneal injection of ovalbumin (OVA) mixed with aluminum hydrochloride at days 1 and 15. Airway sensitization was done by inhalation of 1% OVA solution for 2 weeks from day 23 to 36, or for 4 weeks from day 23 to 50. Nonspecific airway responses to methacholine and OVA-specific airway responses were measured by body pletysmograph (Buxco) at day 22 or day 37, and at day 26 or day 37, respectively.【Results】 There was no significant difference in immediate airway responses to OVA between wild and BXO mice three days or ten days after the initiation of sensitization with OVA inhalation. Similar results were obtained for nonspecific airway responses to methacholine inhalation. No significant difference was observed for serum levels of OVA-specific IgE and IgG, and for bronchoalveolar lavage findings between the two strains. No significant difference was found for airway responses even in 4-week sensitization mice between the two strains ; however, serum levels of OVA-specific IgG were significantly increased in BXO mice.【Discussion】 We have failed to find distinct differences in airway responses in the current study. We should evaluate airway responses also by measuring intratracheal pressure not by body pletysmography. We should also verify the existence of altered content of HA or SHAP as a prerequisite of pathological changes in airways.