Basic research in pathophysiological mechanisms on airway hypersensitivity

本研究旨在阐明BHS和BHR的气道反应性特征，并从体内和体外实验来评价其气道反应性。在体内，用呼吸阻力(RRS)、比气道电导(SGAW)、动态顺应性(Cdyn)和潮气量(Vr)来测量对ACh和组胺雾化吸入的反应。此外，还研究了柠檬酸诱导的咳嗽反射，以阐明呼吸道过敏与咳嗽的关系。在体外，研究了ACh、CCH和组胺对BHS和GHR气管和肺实质的收缩反应。结果表明，BHS的气道反应明显高于BHR，BHS的气道反应模式为RRS增加，Vr、Sgaw和Cdyn降低，而BHR的气道反应模式为RRS减少，Vr、Sgaw和Cdyn增加。BHS对ACh的收缩反应明显大于BHR，但对CCH和组织吻合素的收缩反应不明显。因此，BHS的AChE活性降低可能与BHS和BHR的收缩能力不同有关。这些结果表明，BHS体内对ACH的高反应性是通过增加气道平滑肌的反应性和降低AChE活性来降解ACh而实现的。此外，柠檬酸诱导的咳嗽反射在BHS和BHR中不同，因此，气道敏感性的差异可能影响咳嗽的发生。由于我们可以从不同的角度显示BHS和BHR的气道反应性特征，我们相信这些先天动物模型可能有助于推进哮喘的研究。

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.