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Basic research in pathophysiological mechanisms on airway hypersensitivity

气道过敏病理生理机制基础研究

基本信息

批准号：
07456132
负责人：
SUGANO Shigeru
金额：
$ 4.86万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1997
项目状态：
已结题

项目摘要

The present study was aimed to clarify the characteristics of the airway responses on BHS and BHR.For this purpose, airway responsiveness was evaluated from in vivo and in vitro experiments. In vivo, bronchoconstrictive responses were measured using respiratory resistance (Rrs) , specific airways conductance (SGaw) , dynamic compliance (Cdyn) , and tidal volume (V_r) , to ACh and histamine aerosol inhalation. Moreover, citric acid induced cough reflex was investigated to clarify the relationship between airway hypersensitivity and cough. In vitro, contractile responses to ACh, CCh, and histamine on trachea and lung prenchyma in BHS and GHR were investigated. The results showed that BHS had significantly greater airway responses compared with BHR.Airway response pattern in BHS was an increase in Rrs, decreases in V_r, SGaw and Cdyn, but that in BHR was decrease in Rrs, increaes in V_r, SGaw and Cdyn. It seems that the vagal reflex mechanism for these airwayh responses might be much important in BHS than in BHR.The contractile responses to ACh in the tracheal smooth muscle of BHS were significantly larger than those in BHR,but not to CCh and histomine. Therefore, the reduced AChE activity in the airway might be dependent on the differences in the contractility between BHS and BHR.These results suggests that the hyperresponsivness to ACH in BHS in vivo was resurlted from increased airway smooth muscle responsiveness and decreased AChE activity for degradation of ACh. Further, citric acid-induced cough reflex was different between BHS and BHR.Therefore, the difference of airway sensitivity might be affect the occurrence of cough. Because we could show the characteristics of airway responsiveness from some different poin view in BHS and BHR,we believe that these congenital animal model may be useful for advance of the asthma research.

本研究旨在探讨BHS和BHR气道反应性的特点，并从体内外两方面对气道反应性进行评价。在体实验中，采用呼吸阻力（Rrs）、气道比传导率（SGaw）、动态顺应性（Cdyn）和潮气量（V_r）等指标，测定ACh和组胺对支气管收缩的影响。此外，研究了柠檬酸诱导的咳嗽反射，以阐明气道过敏与咳嗽的关系。在离体条件下，研究了乙酰胆碱（ACh）、胆碱（CCh）和组胺对BHS和GHR气管和肺实质的收缩反应。结果表明，BHS的气道反应性明显大于BHR，BHS的气道反应性为Rrs增加，V_r、SGaw和Cdyn降低，而BHR的气道反应性为Rrs减少，V_r、SGaw和Cdyn增加。BHS的气管平滑肌对ACh的收缩反应明显大于BHR，而对CCh和组胺的收缩反应不明显。因此，BHS和BHR的收缩性差异可能是导致气道AChE活性降低的原因，提示BHS对ACh的高反应性是由于气道平滑肌反应性增强和AChE活性降低而引起的。此外，BHS和BHR对柠檬酸诱发的咳嗽反应不同，因此，气道敏感性的差异可能影响咳嗽的发生。由于BHS和BHR动物模型能从不同角度反映气道反应性的特点，我们认为这一先天性动物模型可能有助于哮喘研究的进一步发展。