【摘要】 实验目的是研究速激肽与哮喘的关系，评价速激肽受体拮抗剂对哮喘的治疗作用。结果表明，ｉｐ速激肽ＮＫ１受体拮抗剂ＣＰ９６３４５，ＮＫ２受体拮抗剂ＳＲ４８９６８或两药合用，均可有效减少清醒致敏豚鼠吸入抗原引起的喘息反应，降低过敏性休克死亡率。ＳＲ４８９６８减轻麻醉豚鼠抗原引起的气道收缩，并浓度依赖性降低抗原引起的气管和支气管平滑肌收缩幅度。ＣＰ９６３４５可抑制抗原诱导的支气管和肺叶伊文思蓝渗出，仅对支气管平滑肌收缩有部分抑制作用。结果提示，速激肽参与哮喘发病，速激肽受体拮抗剂可抑制抗原诱导的气道平滑肌收缩（ＮＫ２受体）和微血管渗漏（ＮＫ１受体）而减轻哮喘反应。更多还原

【Abstract】 In conscious sensitized guinea pigs, CP 96345(2 06 μmol·kg -1 , ip), a specific antagonist for tachykinin NK 1 receptors, SR 48968(1 66 μmol·kg -1 , ip), an NK 2 receptor antagonist, and the combination of both agents decreased the wheezing percentage and the mortality from anaphylactic shock induced by 0 25% ovalbumin (OA, for 0 5 or 2 min) aerosol inhalation. In the anesthetized guinea pigs, SR 48968 attenuated OA (5 mg·kg -1 , iv) induced bronchoconstriction, while CP 96345 inhibited OA induced Evans blue extravasation in bronchi and intrapulmonary airways. In the isolated tracheal and bronchial smooth muscle preparations of guinea pigs, SR 48968 concentration dependently inhibited OA (10 μg·ml -1 ) induced contraction both in trachea and in bronchi, while CP 96345 only attenuated the contraction of bronchi. Pretreatment with capsaicin, a depleting agent of sensory neuropeptides from sensory nerve C fibers, attenuated the OA induced contractions both in trachea and in bronchi. The results indicate that (1) tachykinins in the airways are involved in the pathogenesis of allergic asthma; (2) tachykinin receptor antagonists have inhibitory effects on the allergic asthmatic responses, which is at least partly through the inhibition of antigen induced contraction of airway smooth muscles (NK 2 receptor effect) and airway microvascular leakage (NK 1 receptor effect).更多还原