使用强迫振荡法对变应性豚鼠鼻阻塞的特征化研究。

McLeod Robbie L, Young Simon S, Erickson Christine H, Parra Leonard E, Hey John A

Department of Allergy, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033-0539, USA.

J Pharmacol Toxicol Methods. 2002 Nov-Dec;48(3):153-9. doi: 10.1016/S1056-8719(03)00044-3.

INTRODUCTION

This is the first report to evaluate changes in nasal resistance in a preclinical animal model using the forced oscillation method.

METHODS

The method involves characterizing pressure-flow relationships of the respiratory system due to external oscillatory forces.

RESULTS

First, we evaluated changes in nasal resistance using an established small-animal rhinometric technique. In these studies, aerosolized ovalbumin (3%) administered to the nasal cavity of ovalbumin-sensitized guinea pigs increased nasal resistance at 30 min by 99 +/- 14%. The histamine H1 antagonists, chlorpheniramine (1 mg/kg i.v.) and pyrilamine (1 mg/kg i.v.), blocked the increase in nasal resistance due to ovalbumin provocation (50 +/- 17% and 39 +/- 11% over baseline, respectively). The alpha-adrenergic agonist phenylpropanolamine (3 mg/ kg i.v.) had no effect on the nasal actions of ovalbumin. In separate studies, nasal resistance was measured at 2 Hz by forced oscillation and ovalbumin (3%) increased nasal resistance by 91 +/- 14%. Chlorpheniramine (1 mg/kg i.v.) significantly attenuated the increase in nasal resistance due to ovalbumin. Finally, changes in nasal resistance for each treatment group were evaluated at frequencies of 1 - 18 Hz. Area under the curve analysis demonstrated that chlorpheniramine blocked the nasal obstructive effect of ovalbumin. In contrast, a pharmacologically active dose of phenylpropanolamine (3 mg/kg i.v.) did not produce decongestant activity.

DISCUSSION

The current data are inconsistent with the well-established clinical efficacy of alpha-adrenergic agonists as nasal decongestants. Consequently, we suggest that allergic nasal obstruction in the guinea pig may not be the best preclinical approach to assess the nasal decongestant activity of vasoconstrictor alpha-adrenergic agonists. Additionally, our studies demonstrate the utility of the forced oscillation technique in assessing changes in nasal resistance in small laboratory animals.

引言

这是首份运用强迫振荡法评估临床前动物模型鼻阻力变化的报告。

方法

该方法涉及表征因外部振荡力导致的呼吸系统压力-流量关系。

结果

首先，我们使用既定的小动物鼻测量技术评估鼻阻力变化。在这些研究中，给卵清蛋白致敏的豚鼠鼻腔施用雾化的卵清蛋白（3%），30分钟时鼻阻力增加了99±14%。组胺H1拮抗剂氯苯那敏（1毫克/千克静脉注射）和吡苄明（1毫克/千克静脉注射）可阻断因卵清蛋白激发导致的鼻阻力增加（分别比基线高50±17%和39±11%）。α-肾上腺素能激动剂去氧肾上腺素（3毫克/千克静脉注射）对卵清蛋白的鼻作用无影响。在单独的研究中，通过强迫振荡在2赫兹下测量鼻阻力，卵清蛋白（3%）使鼻阻力增加了91±14%。氯苯那敏（1毫克/千克静脉注射）显著减弱了因卵清蛋白导致的鼻阻力增加。最后，在1至18赫兹的频率下评估每个治疗组的鼻阻力变化。曲线下面积分析表明氯苯那敏阻断了卵清蛋白的鼻阻塞作用。相比之下，药理活性剂量的去氧肾上腺素（3毫克/千克静脉注射）未产生减充血活性。