Erjefält I, Greiff L, Alkner U, Persson C G
Department of Pharmacology, Astra-Draco AB, Lund, Sweden.
Am Rev Respir Dis. 1993 Sep;148(3):695-701. doi: 10.1164/ajrccm/148.3.695.
In this study involving sensitized guinea pigs (anesthetized intramuscularly with a 3:2 mixture of ketamine+xylazine, 1 ml/kg), we applied allergen (ovalbumin) selectively to the tracheobronchial mucosa (sparing the nasal passages and the terminal airways) and examined the occurrence of immediate and late-phase inflammatory exudation of plasma and plasma-derived mediators (bradykinins) into the airway lumen. The experiments were terminated 10 to 480 min after challenge. A selective lavage that sampled the surface liquids of the extrapulmonary bronchi and the lower trachea was performed. The amount of plasma (microliter) was determined by analysis of a plasma tracer, [125I]albumin, in lavage fluid and blood (plasma) samples. Ovalbumin, 3 to 12 pmol, and histamine, 5 and 10 nmol, produced a dose-dependent immediate exudation response (p < 0.001). The effects were nonneurogenic because they were not affected by topical lidocaine given in a dose (3 nmol) that prevented the exudative effect of capsaicin. The 6- and 12-pmol doses of ovalbumin (but not 3 pmol) produced a significant late-phase exudative response at 5 h (p < 0.001), and both the immediate and late phases were associated with increased (p < 0.01 to p < 0.001) levels of bradykinin in the lavage fluids. Histamine, even in doses that produced a greater early response than the allergen, did not produce a late-phase response. A single topical dose of an antiasthma steroid (budesonide, 12 mumol/kg) administered just before ovalbumin (6 pmol) had little effect on the immediate response but inhibited the late-phase response (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
在这项涉及致敏豚鼠的研究中(用氯胺酮+赛拉嗪3:2混合物进行肌肉注射麻醉,1毫升/千克),我们将变应原(卵清蛋白)选择性地应用于气管支气管黏膜(避开鼻道和终末气道),并检测血浆及血浆源性介质(缓激肽)即刻和迟发性炎症渗出至气道腔的情况。激发后10至480分钟终止实验。进行选择性灌洗以采集肺外支气管和下气管的表面液体。通过分析灌洗液和血液(血浆)样本中的血浆示踪剂[125I]白蛋白来测定血浆量(微升)。3至12皮摩尔的卵清蛋白以及5和10纳摩尔的组胺产生了剂量依赖性的即刻渗出反应(p<0.001)。这些效应是非神经源性的,因为它们不受剂量为3纳摩尔的局部利多卡因的影响,而该剂量的利多卡因可阻止辣椒素的渗出效应。6皮摩尔和12皮摩尔剂量的卵清蛋白(但3皮摩尔剂量的未出现)在5小时时产生了显著的迟发性渗出反应(p<0.001),即刻和迟发阶段均与灌洗液中缓激肽水平升高(p<0.01至p<0.001)相关。组胺即使在产生比变应原更大早期反应的剂量下,也未产生迟发性反应。在卵清蛋白(6皮摩尔)给药前单次局部给予抗哮喘类固醇(布地奈德,12微摩尔/千克)对即刻反应影响不大,但抑制了迟发性反应(p<0.01)。(摘要截短于250字)