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在小鼠屋尘螨诱导的哮喘模型中,膳食低聚半乳糖可预防气道嗜酸性粒细胞增多和高反应性。

Dietary galacto-oligosaccharides prevent airway eosinophilia and hyperresponsiveness in a murine house dust mite-induced asthma model.

作者信息

Verheijden Kim A T, Willemsen Linette E M, Braber Saskia, Leusink-Muis Thea, Delsing Dianne J M, Garssen Johan, Kraneveld Aletta D, Folkerts Gert

出版信息

Respir Res. 2015 Feb 7;16(1):17. doi: 10.1186/s12931-015-0171-0.

Abstract

BACKGROUND

Allergic asthma is strongly associated with the exposure to house dust mite (HDM) and is characterized by eosinophilic pulmonary inflammation and airway hyperresponsiveness (AHR). Recently, there is an increased interest in using dietary oligosaccharides, also known as prebiotics, as a novel strategy to prevent the development of, or reduce, symptoms of allergy.

AIM

We investigated the preventive capacity of dietary galacto-oligosaccharides (GOS) compared to an intra-airway therapeutic treatment with budesonide on the development of HDM-induced allergic asthma in mice.

METHODS

BALB/c mice were intranasally sensitized with 1 μg HDM on day 0 followed by daily intranasal challenge with PBS or 10 μg HDM on days 7 to 11. Two weeks prior to the first sensitization and throughout the experiment mice were fed a control diet or a diet containing 1% GOS. Reference mice were oropharyngeally instilled with budesonide (500 μg/kg) on days 7, 9, 11, and 13, while being fed the control diet. On day 14, AHR was measured by nebulizing increasing doses of methacholine into the airways. At the end of the experiment, bronchoalveolar lavage fluid (BALF) and lungs were collected.

RESULTS

Sensitization and challenge with HDM resulted in AHR. In contrast to budesonide, dietary intervention with 1% GOS prevented the development of AHR. HDM sensitization and challenge resulted in a significant increase in BALF leukocytes numbers, which was suppressed by budesonide treatment and dietary intervention with 1% GOS. Moreover, HDM sensitization and challenge resulted in significantly enhanced concentrations of IL-6, CCL17, IL-33, CCL5 and IL-13 in lung tissue. Both dietary intervention with 1% GOS or budesonide treatment significantly decreased the HDM-induced increased concentrations of CCL5 and IL-13 in lung tissue, while budesonide also reduced the HDM-enhanced concentrations of IL-6 and CCL17 in lung tissue.

CONCLUSION

Not only did dietary intervention with 1% GOS during sensitization and challenge prevent the induction of airway eosinophilia and Th2-related cytokine and chemokine concentrations in the lung equally effective as budesonide treatment, it also prevented AHR development in HDM-allergic mice. GOS might be useful for the prevention and/or treatment of symptoms in asthmatic disease.

摘要

背景

过敏性哮喘与接触屋尘螨(HDM)密切相关,其特征为嗜酸性粒细胞性肺部炎症和气道高反应性(AHR)。最近,人们越来越关注使用膳食低聚糖(也称为益生元)作为预防过敏发展或减轻过敏症状的新策略。

目的

我们研究了膳食低聚半乳糖(GOS)与布地奈德气道内治疗相比,对小鼠HDM诱导的过敏性哮喘发展的预防能力。

方法

BALB/c小鼠在第0天经鼻用1μg HDM致敏,随后在第7至11天每天经鼻用PBS或10μg HDM激发。在首次致敏前两周及整个实验过程中,给小鼠喂食对照饮食或含1% GOS的饮食。参照小鼠在第7、9、11和13天经口咽滴注布地奈德(500μg/kg),同时喂食对照饮食。在第14天,通过向气道雾化递增剂量的乙酰甲胆碱来测量AHR。在实验结束时,收集支气管肺泡灌洗液(BALF)和肺组织。

结果

HDM致敏和激发导致AHR。与布地奈德不同,1% GOS的膳食干预可预防AHR的发展。HDM致敏和激发导致BALF白细胞数量显著增加,布地奈德治疗和1% GOS的膳食干预可抑制这一增加。此外,HDM致敏和激发导致肺组织中IL-6、CCL17、IL-33、CCL5和IL-13的浓度显著升高。1% GOS的膳食干预或布地奈德治疗均显著降低了HDM诱导的肺组织中CCL5和IL-13浓度的升高,而布地奈德还降低了HDM增强的肺组织中IL-6和CCL17的浓度。

结论

在致敏和激发过程中,1% GOS的膳食干预不仅在预防肺部气道嗜酸性粒细胞增多以及Th2相关细胞因子和趋化因子浓度方面与布地奈德治疗同样有效,还能预防HDM过敏性小鼠AHR的发展。GOS可能对哮喘疾病症状的预防和/或治疗有用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f057/4327967/b390f06460a2/12931_2015_171_Fig1_HTML.jpg

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