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卵清蛋白致敏的小鼠是气道高反应性的良好模型,但不是吸入过敏原后急性生理反应的良好模型。

Ovalbumin-sensitized mice are good models for airway hyperresponsiveness but not acute physiological responses to allergen inhalation.

作者信息

Zosky G R, Larcombe A N, White O J, Burchell J T, Janosi T Z, Hantos Z, Holt P G, Sly P D, Turner D J

机构信息

Centre for Child Health Research, Telethon Institute for Child Health Research, University of Western Australia, Perth, WA, Australia.

出版信息

Clin Exp Allergy. 2008 May;38(5):829-38. doi: 10.1111/j.1365-2222.2007.02884.x. Epub 2007 Dec 7.

Abstract

BACKGROUND

Asthma is a chronic inflammatory disease that is characterized clinically by airway hyperresponsiveness (AHR) to bronchoconstricting agents. The physiological response of the asthmatic lung to inhaled allergen is often characterized by two distinct phases: an early-phase response (EPR) within the first hour following exposure that subsides and a late-phase response (LPR) that is more prolonged and may occur several hours later. Mouse models of asthma have become increasingly popular and should be designed to exhibit an EPR, LPR and AHR.

OBJECTIVE

To determine whether a common model of asthma is capable of demonstrating an EPR, LPR and AHR.

METHODS

BALB/c mice were sensitized to ovalbumin (OVA) and challenged with one or three OVA aerosols. Changes in lung mechanics in response to allergen inhalation were assessed using a modification of the low-frequency forced oscillation technique (LFOT). In order to assess AHR, changes in lung mechanics in response to aerosolized methacholine were assessed using LFOT. Inflammatory cell infiltration into the lung was measured via bronchoalveolar lavage (BAL). ELISAs were used to measure inflammatory cytokines in the BAL and levels of IgE in the serum.

RESULTS

An EPR was only detectable after three OVA aerosols in approximately half of the mice studied. There was no evidence of an LPR despite a clear increase in cellular infiltration 6 h post-allergen challenge. AHR was present after a single OVA aerosol but not after three OVA aerosols.

CONCLUSIONS

The lack of an LPR, limited EPR and the absence of a link between the LPR and AHR highlight the limitations of this mouse model as a complete model of the lung dysfunction associated with asthma.

摘要

背景

哮喘是一种慢性炎症性疾病,临床上以气道对支气管收缩剂的高反应性(AHR)为特征。哮喘患者肺部对吸入变应原的生理反应通常表现为两个不同阶段:暴露后第一小时内出现的早期反应(EPR),随后消退;以及更持久的晚期反应(LPR),可能在数小时后出现。哮喘小鼠模型越来越受欢迎,其设计应能表现出EPR、LPR和AHR。

目的

确定一种常见的哮喘模型是否能够表现出EPR、LPR和AHR。

方法

将BALB/c小鼠用卵清蛋白(OVA)致敏,并用一次或三次OVA气雾剂进行激发。使用低频强迫振荡技术(LFOT)的改良方法评估吸入变应原后肺力学的变化。为了评估AHR,使用LFOT评估雾化乙酰甲胆碱后肺力学的变化。通过支气管肺泡灌洗(BAL)测量肺内炎性细胞浸润。酶联免疫吸附测定(ELISA)用于测量BAL中的炎性细胞因子和血清中的IgE水平。

结果

在大约一半接受研究的小鼠中,仅在三次OVA气雾剂激发后可检测到EPR。尽管在变应原激发后6小时细胞浸润明显增加,但没有LPR的证据。单次OVA气雾剂激发后存在AHR,但三次OVA气雾剂激发后不存在。

结论

缺乏LPR、有限的EPR以及LPR与AHR之间缺乏关联,突出了该小鼠模型作为哮喘相关肺功能障碍完整模型的局限性。

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