ROLE OF EICOSANOIDS IN AIRWAY HYPERRESPONSIVENESS

呼吸道高反应性是人类哮喘的一个特征， 其他肺部疾病的数量，包括病毒感染和吸烟 吸烟引起的支气管炎。最近的证据表明，激活 内源性花生四烯酸代谢可能在 呼吸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发病机制中的作用 自发性可逆性呼吸道模型中的高反应性 小马上的障碍物。这种肺部疾病模型是独一无二的，因为 马科动物是唯一一种自发发展成周期性的家养动物 与哮喘相似的呼吸道阻塞和高反应性 人类。 本提案的具体目标是：1)确定 马匹的支气管肺泡灌洗和血浆二十烷基类化合物水平 临床缓解期和干草尘后再发支气管痉挛 在他们的年龄和性别匹配的对照中；2)确定 抑制磷脂酶A2、环氧合酶或白三烯的作用 生物合成对呼吸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二十烷基类化合物浓度 在临床缓解期间和暴露于干草粉尘后以及在他们的年龄 和性别匹配的对照组；3)确定对呼吸道的影响 归因于内源性二十烷类化合物的高反应性可以复制 通过向委托人外源给予适当的二十烷类化合物 疾病缓解期的小马，以及年龄和性别匹配的对照组。 动态顺应性，肺阻力，强迫振荡电导， 功能残气量和血气紧张将在 意识清醒的小马作为大小气道口径的指示器 将生成乙酰甲胆碱剂量-反应曲线以评估呼吸道 响应性。血浆和支气管肺泡灌洗液将被检测 用放射免疫测定法和高效液体测定二十烷类化合物 层析法。 这些研究将增加对二十烷类化合物在 呼吸道高反应性，并可能导致改进措施，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.