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气道中的粘液产生和睫状性粉刺而与哮喘的发病机理有关。为了直接证明这一假设，我们使用Bikunin敲除（BXO）小鼠研究了气道响应能力，这对于血清衍生的透明质酸相关蛋白（SHAP）的转移反应至关重要。 [方法]我们使BXO小鼠形成DBA1或BALBC菌株。我们在第1和15天对腹膜内注射椭圆蛋白（OVA）与盐酸铝混合的敏感小鼠敏感。通过吸入1％OVA溶液从23到36天，从23至36的4周中吸入1％OVA溶液，从23到50次进行了甲基甲基甲基甲基甲基反应。 （BUXCO）分别在第22天或第37天以及第26天或第37天。[结果] [结果]野生和BXO小鼠之间对卵子小鼠的卵子的立即响应没有显着差异，三天或十天后，对OVA吸入的敏感性启发。对于非特异性气道吸入的反应获得了类似的结果。对于OVA特异性IgE和IgG的血清水平以及两种菌株之间的支气管肺泡灌洗发现，没有观察到显着差异。即使在两种菌株之间的4周灵敏度小鼠中，气道反应也没有显着差异。然而，BXO小鼠中OVA特异性IgG的血清水平显着升高。 [讨论]在当前研究中，我们未能发现气道响应的明显差异。我们应该还应通过测量气管内压力来评估气道反应，而不是通过人体杂质记录。我们还应该验证HA或Shap含量改变的存在，这是气道病理变化的先决条件。