ROLE OF EICOSANOIDS IN AIRWAY HYPERRESPONSIVENESS

气道高反应性是人类哮喘的特征性特征， 一些其他肺部疾病，包括病毒感染和吸烟 吸烟引起支气管炎。 最近的证据表明， 内源性花生四烯酸代谢可能在 气道高反应性的病理生理学。 这个项目的总体目标是 建议研究环氧合酶和脂氧合酶的作用 花生四烯酸代谢产物在呼吸道疾病发病中的作用 可逆性气道自发性高反应性模型 小马的障碍物。 这种肺部疾病的模型是独一无二的， 马科动物是唯一的家畜， 与哮喘相似的气道阻塞和气道高反应性， 人类 本提案的具体目标是：（1）确定 支气管肺泡灌洗和血浆类花生酸水平 临床缓解期和干草尘后复发性支气管痉挛 暴露及其年龄和性别匹配的对照; 2）确定 抑制磷脂酶A2、环氧合酶或白三烯的作用 生物合成对气道反应性和支气管肺泡灌洗的影响， 复发性支气管痉挛小马的血浆类花生酸浓度 在临床缓解期和干草尘暴露后， 3）确定是否对气道的影响， 内源性类二十烷酸引起的高反应性可以复制 通过向主体外源性施用适当的类二十烷酸， 疾病缓解的小马和他们的年龄和性别匹配的控制。 动态顺应性，肺阻力，强迫振荡电导， 将测量功能残气量和血气张力， 有意识的小马作为大和小气道口径的指标， 将生成乙酰甲胆碱剂量-反应曲线，以评估气道 响应能力。 将测定血浆和支气管肺泡灌洗液 放射免疫分析法和高效液相色谱法测定类花生酸 层析 这些研究将增加对类二十烷酸在 气道高反应性，并可能导致改善措施，以防止或 治疗人类哮喘

Airway hyperreactivity is a characteristic feature of human asthma and a number of other lung diseases including viral infections, and cigarette smoke induced bronchitis. Recent evidence suggests that activation of endogenous arachidonate metabolism may play an important role in the pathophysiology of airway hyperresponsiveness. The overall goal of this proposal is to investigate the role of cyclooxygenase and lipoxygenase products of arachidonate metabolism in the pathogenesis of airway hyperresponsiveness in a spontaneously occurring model of reversible airway obstruction in the pony. This model of lung disease is unique because equids are the only domestic animals which spontaneously develop recurrent airway obstruction and airway hyperresponsiveness similar to asthma in humans. The specific objectives of this proposal are 1) to determine bronchoalveolar lavage and plasma levels of eicosanoids in ponies with recurrent bronchospasm during clinical remission and following hay dust exposure and in their age and gender-matched controls; 2) to determine the effect of inhibiting phospholipase A2, cyclooxygenase or leukotriene biosynthesis on airway responsiveness, and bronchoalveolar lavage and plasma eicosanoid concentrations in ponies with recurrent bronchospasm during clinical remission and following hay dust exposure and in their age and gender-matched controls; 3) to determine if the effects on airway hyperresponsiveness attributed to endogenous eicosanoids can be duplicated by exogenous administration of the appropriate eicosanoid to principal ponies in disease remission and to their age and gender-matched controls. Dynamic compliance, pulmonary resistance, forced oscillating conductance, functional residual capacity and blood gas tensions will be measured in conscious ponies as indicators of large and small airway caliber while methacholine dose-response curves will be generated to assess airway responsiveness. Plasma and bronchoalveolar lavage fluid will be assayed for eicosanoids using radioimmunoassay and high performance liquid chromatography. These studies will increase understanding of the role of eicosanoids in airway hyperresponsiveness and may lead to improved measures to prevent or treat human asthma.