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

使用 Bikunin 基因敲除小鼠进行哮喘模型气道重塑的研究。

• 批准号: 17590807
• 负责人: YAMAGUCHI Etsuro
• 金额: $ 1.98万
• 依托单位: Aichi Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590807/
• 关键词: bronchial asthma; remodeling; hyarulonan; bikunin; airway hyperreactivity; SHAP; knock out mouse; ovalbumin

【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.

[目的]透明质酸可能通过影响呼吸道粘液产生和纤毛搏动参与哮喘的发病。为了直接证明这一假设，我们用Bikunin基因敲除(BXO)小鼠研究了BXO小鼠的气道反应性，这是血清来源的透明质酸相关蛋白(Shap)转移反应所必需的。分别于第1天和第15天用卵白蛋白(OVA)与盐酸铝混合注射致敏小鼠，第23~36天吸入1%OVA溶液2周，第23~50天连续4周致敏。分别在第22天、37天、26天、37天用BUXCO法检测小鼠对乙酰胆碱的非特异性气道反应和OVA特异性的气道反应。吸入乙酰甲胆碱的非特异性呼吸道反应也得到了类似的结果。血清OVA特异性IgE和Ig G水平以及支气管肺泡灌洗结果在两个菌株之间没有显著差异。两个品系致敏小鼠的呼吸道反应即使在4周内也没有显著差异，但BXO小鼠血清OVA特异性免疫球蛋白水平显著升高。[讨论]在本研究中，我们没有发现明显的呼吸道反应差异。我们也应该通过测量气管内压力来评估呼吸道反应，而不是通过身体体积描记。我们还应验证是否存在HA或Shap含量改变，作为呼吸道病变的先决条件。