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双酚A对实验小鼠模型哮喘发展的终生依赖性影响。

Lifetime-dependent effects of bisphenol A on asthma development in an experimental mouse model.

作者信息

Petzold Susanne, Averbeck Marco, Simon Jan C, Lehmann Irina, Polte Tobias

机构信息

UFZ - Helmholtz Centre for Environmental Research Leipzig-Halle, Department of Environmental Immunology, Leipzig, Germany; Department of Dermatology, Venerology and Allergology, Leipzig University Medical Center, Leipzig, Germany.

Department of Dermatology, Venerology and Allergology, Leipzig University Medical Center, Leipzig, Germany.

出版信息

PLoS One. 2014 Jun 20;9(6):e100468. doi: 10.1371/journal.pone.0100468. eCollection 2014.

Abstract

BACKGROUND

Environmental factors are thought to contribute significantly to the increase of asthma prevalence in the last two decades. Bisphenol A (BPA) is a xenoestrogen commonly used in consumer products and the plastic industry. There is evidence and an ongoing discussion that endocrine disruptors like BPA may affect human health and also exert alterations on in the immune system. The aim of this study was to investigate age-dependent effects of BPA on the asthma risk using a murine model to explain the controversial results reported till date.

METHODS

BALB/c mice were exposed to BPA via the drinking water for different time periods including pregnancy and breastfeeding. To induce an asthma phenotype, mice were sensitized to ovalbumin (OVA), followed by an intrapulmonary allergen challenge.

RESULTS

BPA exposure during pregnancy and breastfeeding had no significant effect on asthma development in the offspring. In contrast, lifelong exposure from birth until the last antigen challenge clearly increased eosinophilic inflammation in the lung, airway hyperreactivity and antigen-specific serum IgE levels in OVA-sensitized adult mice compared to mice without BPA exposure. Surprisingly, BPA intake during the sensitization period significantly reduced the development of allergic asthma. This effect was reversed in the presence of a glucocorticoid receptor antagonist.

CONCLUSIONS

Our results demonstrate that the impact of BPA on asthma risk is strongly age-dependent and ranges from asthma-promoting to asthma-reducing effects. This could explain the diversity of results from previous studies regarding the observed health impact of BPA.

摘要

背景

环境因素被认为在过去二十年中对哮喘患病率的增加有显著贡献。双酚A(BPA)是一种常用于消费品和塑料工业的外源性雌激素。有证据表明且正在进行的讨论指出,像BPA这样的内分泌干扰物可能会影响人类健康,并且还会对免疫系统产生改变。本研究的目的是使用小鼠模型研究BPA对哮喘风险的年龄依赖性影响,以解释迄今为止报道的有争议的结果。

方法

将BALB/c小鼠在包括怀孕和哺乳期的不同时间段通过饮用水暴露于BPA。为诱导哮喘表型,使小鼠对卵清蛋白(OVA)致敏,随后进行肺内过敏原激发。

结果

怀孕和哺乳期暴露于BPA对后代的哮喘发展没有显著影响。相比之下,与未暴露于BPA的小鼠相比,从出生到最后一次抗原激发的终身暴露明显增加了OVA致敏成年小鼠的肺部嗜酸性粒细胞炎症、气道高反应性和抗原特异性血清IgE水平。令人惊讶的是,致敏期摄入BPA显著降低了过敏性哮喘的发展。在存在糖皮质激素受体拮抗剂的情况下,这种作用被逆转。

结论

我们的结果表明,BPA对哮喘风险的影响强烈依赖于年龄,范围从促进哮喘到减轻哮喘的作用。这可以解释先前关于BPA对健康影响的研究结果的多样性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a69/4065062/e352febcd6b0/pone.0100468.g001.jpg

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