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重复柠檬酸暴露诱导豚鼠咳嗽模型气道重塑和持续性咳嗽。

Induction of airway remodeling and persistent cough by repeated citric acid exposure in a guinea pig cough model.

机构信息

Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Japan; Department of Respiratory Medicine, Huadong Hospital, Fudan University, Shanghai, China.

Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Japan.

出版信息

Respir Physiol Neurobiol. 2019 May;263:1-8. doi: 10.1016/j.resp.2019.02.002. Epub 2019 Feb 7.

DOI:10.1016/j.resp.2019.02.002
PMID:30738972
Abstract

BACKGROUND

A previous study involving guinea pigs showed that repeated cough could increase peripheral airway smooth muscle area, which can also aggravate cough. The airway pathologic changes produced by prolonged cough are still unknown.

OBJECTIVE

To study the airway pathologic changes in prolonged cough models of guinea pigs.

METHODS

Guinea pigs were assigned to three treatment groups: citric acid inhalation (CA) alone, citric acid inhalation with codeine pretreatment (COD), or saline solution inhalation (SA). Animals were challenged with citric acid or saline solution three times weekly. The intervention period was 22 or 43 days. Animals were challenged with citric acid on the first and last days of exposure. Lung specimens were obtained for pathologic analysis 72 h after the last exposure.

RESULTS

Compared with the other two groups, the CA group had increased frequency of cough on both 22 and 43 days of exposure. Tracheal basement membrane (BM) thickness was increased after 43 days of exposure, correlating with the frequency of cough. The area of airway smooth muscles (ASM index) in small airways increased in the CA group after both 22 and 43 days of exposure, compared with the SA group. Compared with the COD group, the ASM index in small airways increased in the CA group after 22 days of exposure instead of 43 days of exposure.

CONCLUSIONS

An increase in peripheral smooth muscle area by repeated cough was confirmed. Moreover, this is the first study to show that tracheal BM thickness increased after prolonged exposure (43 days). Repeated cough may lead to airway remodeling, which was also associated with an increased frequency of cough.

摘要

背景

先前的豚鼠研究表明,反复咳嗽会增加外周气道平滑肌面积,从而加重咳嗽。但持续咳嗽引起的气道病理变化尚不清楚。

目的

研究豚鼠持续性咳嗽模型中的气道病理变化。

方法

豚鼠分为柠檬酸吸入(CA)组、柠檬酸联合可待因预处理(COD)组和生理盐水吸入(SA)组。动物每周接受柠檬酸或生理盐水处理 3 次,干预周期为 22 或 43 天。在暴露的第 1 天和最后 1 天接受柠檬酸刺激。末次暴露后 72 h 收集肺标本进行病理分析。

结果

与其他两组相比,CA 组在 22 和 43 天暴露期间咳嗽次数均增加。暴露 43 天后,气管基底膜(BM)厚度增加,与咳嗽频率相关。与 SA 组相比,CA 组在 22 和 43 天暴露后小气道中的气道平滑肌面积(ASM 指数)增加。与 COD 组相比,CA 组在 22 天暴露后而不是 43 天暴露后小气道中的 ASM 指数增加。

结论

本研究证实了反复咳嗽会导致外周平滑肌面积增加。此外,这是第一项表明长期暴露(43 天)后气管 BM 厚度增加的研究。反复咳嗽可能导致气道重塑,这与咳嗽频率增加有关。

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