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苯并[a]芘通过表观遗传重塑对小鼠变应性气道炎症的影响。

The impact of benzo[a]pyrene on murine allergic airway inflammation via epigenetic remodeling.

机构信息

Department of Anesthesiology, Peking University Shenzhen Hospital, Shenzhen, China.

The Department of Anesthesiology, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, China; Department of Anesthesiology, Peking University Shenzhen Hospital, Shenzhen, China.

出版信息

Environ Toxicol Pharmacol. 2022 Jan;89:103782. doi: 10.1016/j.etap.2021.103782. Epub 2021 Dec 7.

Abstract

Simultaneous exposure to both BaP and house dust mites (HDM) has been shown to exacerbate pulmonary inflammation and hyperresponsiveness in a murine asthma model. The mechanistic insight into epigenetic inheritance for this effect, however, remains to be clarified. As such, in this study, we explore the molecular basis for the enhancement of asthma. Female BAL/C mice were intranasally administered HDM (25 µg in 25 μL saline) and/or BaP (10 μg/kg) every other day for 9 weeks. RNA sequencing and DNA methylation assessment were used to explore the underlying mechanism. Following simultaneous exposure to HDM and BaP, mice exhibited pulmonary inflammation and the transcript level of IL4i1b, muc4 and IL22ra2 that were associated with altered DNA methylation, suggesting that there may be an epigenetic basis for BaP-induced asthma exacerbation. Our data suggest that DNA methylation is a major epigenetic modification that accompanies airway remodeling associated with changes in the allergic mice.

摘要

同时暴露于苯并芘(BaP)和屋尘螨(HDM)已被证明会在小鼠哮喘模型中加剧肺部炎症和高反应性。然而,对于这种影响的表观遗传继承的机制理解仍有待阐明。因此,在这项研究中,我们探索了增强哮喘的分子基础。雌性 BAL/C 小鼠每隔一天经鼻腔给予 HDM(25μg 在 25μL 盐水中)和/或 BaP(10μg/kg),共 9 周。使用 RNA 测序和 DNA 甲基化评估来探索潜在的机制。在同时暴露于 HDM 和 BaP 后,小鼠表现出肺部炎症和与 DNA 甲基化改变相关的 IL4i1b、muc4 和 IL22ra2 的转录水平,表明 BaP 诱导的哮喘加重可能存在表观遗传基础。我们的数据表明,DNA 甲基化是一种主要的表观遗传修饰,伴随着与过敏小鼠中改变相关的气道重塑。

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