Department of Child and Adolescent Health, School of Public Health, China Medical University, No 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, PR China.
Department of Social Medicine, School of Public Health, China Medical University, No 77 Puhe Road, Shenyang North New Area, Shenyang, Liaoning 110122, PR China.
Chemosphere. 2020 Jun;248:126035. doi: 10.1016/j.chemosphere.2020.126035. Epub 2020 Jan 27.
Epidemiologic studies show that there is a link between Bisphenol A (BPA) exposure and lung inflammation. Despite this, the molecular mechanisms are not entirely known. This study sought to determine whether exposure to BPA affected the development of ovalbumin (OVA) induced lung inflammation in adolescent female mice and whether the mechanism was related to mTOR-mediated autophagy pathway. Female 4-week-old C57BL/6 mice after one week of domestication were randomly divided into five groups (8/group): control group, OVA group, 0.1 μg mL BPA + OVA group, 0.2 μg mL BPA + OVA group and 0.4 μg mL BPA + OVA group. BPA exacerbated airway hyperresponsiveness (AHR), induced the pathological changes in the lung, which also enhanced inflammatory cells and cytokine levels. In addition, BPA exposure affected expression of autophagy associated proteins and genes. This research results indicated that BPA aggravated OVA-induced lung inflammation and induced abnormal immune function in mice, and its mechanism was related to the activation of autophagy pathway by down-regulation expression of mTOR. These findings suggest that therapeutic strategies to target autophagy may offer a new approach for severe asthma therapy.
流行病学研究表明，双酚 A（BPA）暴露与肺部炎症之间存在关联。尽管如此，其分子机制尚不完全清楚。本研究旨在确定 BPA 暴露是否会影响青春期雌性小鼠卵清蛋白（OVA）诱导的肺部炎症的发展，以及其机制是否与 mTOR 介导的自噬途径有关。经过一周驯化的 4 周龄雌性 C57BL/6 小鼠被随机分为五组（每组 8 只）：对照组、OVA 组、0.1μg/mL BPA+OVA 组、0.2μg/mL BPA+OVA 组和 0.4μg/mL BPA+OVA 组。BPA 加重了气道高反应性（AHR），诱导了肺部的病理变化，还增强了炎症细胞和细胞因子水平。此外，BPA 暴露还影响了自噬相关蛋白和基因的表达。这些研究结果表明，BPA 加重了 OVA 诱导的肺部炎症，并导致小鼠免疫功能异常，其机制与 mTOR 表达下调激活自噬途径有关。这些发现表明，针对自噬的治疗策略可能为严重哮喘的治疗提供一种新方法。
