Johnson A, Broadley K J
Division of Pharmacology, Welsh School of Pharmacy, Cardiff University, UK.
Pharmacol Toxicol. 1999 Jun;84(6):281-7. doi: 10.1111/j.1600-0773.1999.tb01495.x.
Actively sensitised guinea-pigs were exposed to inhalation challenges with ovalbumin aerosol (macro- and microshock) and airway responsiveness to six intravenously administered spasmogens was evaluated 18 to 24 hr later in the anaesthetised animal. An increase in airway sensitivity was defined as a significant leftward shift of the dose-response curve when compared with saline-challenged control sensitized animals. After ovalbumin-macroshock (1% ovalbumin for 2 min. with mepyramine cover against fatal anaphylaxis), airway hyperresponsiveness was seen to 5-HT, the thromboxane A2-mimetic, U-46619, and bradykinin but not to methacholine, histamine or substance P. A similar pattern was seen after ovalbumin-microshock (0.010% ovalbumin for 60 min.), with induction of airway hyperreactivity to 5-HT and U-46619 but not methacholine or histamine. When the U-46619 dose-response curve was constructed following treatment of the animals with atropine (1 mg/kg, intravenously), airway hyperresponsiveness was no longer significant. As an index of airway inflammation, lung weights were significantly heavier in ovalbumin-challenged animals, than in saline-challenged controls. The results of this study with intravenously administered spasmogens does not support claims that ovalbumin-induced airway hyperreactivity in the guinea-pig is a 'non-specific' phenomenon.
将主动致敏的豚鼠暴露于卵清蛋白气雾剂吸入激发试验（大剂量和小剂量激发）中，18至24小时后在麻醉动物中评估气道对六种静脉注射的致痉剂的反应性。与盐水激发的对照致敏动物相比，气道敏感性增加定义为剂量反应曲线明显向左移动。在卵清蛋白大剂量激发后（1%卵清蛋白，持续2分钟，用美吡拉敏预防致命性过敏反应），观察到对5-羟色胺、血栓素A2模拟物U-46619和缓激肽出现气道高反应性，但对乙酰甲胆碱、组胺或P物质未出现。在卵清蛋白小剂量激发后（0.010%卵清蛋白，持续60分钟）观察到类似模式，诱导了对5-羟色胺和U-46619的气道高反应性，但对乙酰甲胆碱或组胺未出现。在用阿托品（1毫克/千克，静脉注射）处理动物后构建U-46619剂量反应曲线时，气道高反应性不再显著。作为气道炎症指标，卵清蛋白激发的动物肺重量明显重于盐水激发的对照动物。这项关于静脉注射致痉剂的研究结果不支持关于卵清蛋白诱导豚鼠气道高反应性是一种“非特异性”现象的说法。
