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首页> 外文期刊>Environmental research >Exposure to traffic-generated air pollutants mediates alterations in brain microvascular integrity in wildtype mice on a high-fat diet
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Exposure to traffic-generated air pollutants mediates alterations in brain microvascular integrity in wildtype mice on a high-fat diet

机译：暴露于交通产生的空气污染物会介导高脂饮食的野生型小鼠大脑微血管完整性的变化

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摘要

Air pollution-exposure is associated with detrimental outcomes in the central nervous system (CNS) such as cerebrovascular disorders, including stroke, and neurodegenerative diseases. While the mechanisms of these CNS-related outcomes involved have not been fully elucidated, exposure to traffic-generated air pollutants has been associated with altered blood brain barrier (BBB) integrity and permeability. The current study investigated whether inhalation exposure to mixed vehicle emissions (MVE) alters cerebral microvascular integrity in healthy 3 mo old C57BL/6 mice, as well as whether exposure-mediated effects were exacerbated by a high-fat (HF) vs. low-fat (LF) diet. Mice on each diet were randomly assigned to be exposed to either filtered air (FA) or MVE [100 PM/m~3 vehicle emissions mixture: 30 μg PM/m~3 gasoline engine + 70 μg PM/m~3 diesel engine emissions; median size — 60 nm; particle mass size distribution median of -1 μm (range: < 0.5-20 μm)] for 6 h/d, 7d/wk, for 30d. Using sodium fluorescein as a tracer, we observed a significant increase in BBB permeability in both HF + MVE exposed and HF + FA animals, compared to LF + FA controls. Exposure to HF + MVE also led to a significant increase plasma ox-LDL and ox-LDL scavenger receptors (LOX-1 and CD-36) expression in the cerebral vasculature. Histological analysis revealed decreased expression of TJ protein, claudin-5, associated with increased matrix metalloproteinase (MMP) - 9 activity and oxidative stress in the cerebral vasculature of HF + MVE mice, compared to LF + MVE. Such findings indicate that inhalation exposure to traffic-generated pollutants, coupled with a HF diet, results in altered BBB integrity and increased ox-LDL signaling in the cerebral vasculature in a wildtype animal model.
机译：空气污染暴露与中枢神经系统（CNS）的有害后果有关，例如脑血管疾病（包括中风）和神经退行性疾病。尽管尚未完全阐明这些与中枢神经系统有关的结局的机制，但暴露于交通产生的空气污染物已与血脑屏障（BBB）完整性和通透性改变相关。目前的研究调查了吸入暴露于混合媒介物排放（MVE）是否会改变健康的3个月大的C57BL / 6小鼠的大脑微血管完整性，以及高脂（HF）与低脂（HF）对接触介导的影响是否加剧脂肪（LF）饮食。每种饮食中的小鼠被随机分配到暴露于过滤空气（FA）或MVE中[100 PM / m〜3车辆排放混合物：30μgPM / m〜3汽油发动机+ 70μgPM / m〜3柴油发动机排放;中值尺寸-60 nm；颗粒质量尺寸分布中位数为-1μm（范围：<0.5-20μm）] 6 h / d，7d / wk，30 d。使用荧光素钠作为示踪剂，我们观察到与LF + FA对照相比，暴露于HF + MVE和HF + FA的动物的BBB通透性显着增加。暴露于HF + MVE也会导致脑血管中血浆ox-LDL和ox-LDL清道夫受体（LOX-1和CD-36）的表达显着增加。组织学分析显示，与LF + MVE相比，HF + MVE小鼠的脑血管中TJ蛋白claudin-5的表达减少，与基质金属蛋白酶（MMP）-9活性和氧化应激增加有关。这些发现表明，在野生型动物模型中，吸入交通产生的污染物，再加上HF饮食，会导致BBB完整性的改变和大脑脉管系统中ox-LDL信号的增加。

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  • 来源
    《Environmental research》 |2018年第1期|449-461|共13页
  • 作者

    Usa Suwannasual; JoAnn Lucero; Jacob D. McDonald; Amie K. Lund;

  • 作者单位

    Advanced Environmental Research Institute, Department of Biological Sciences, University of North Texas, Denton, TX 76201, USA;

    Advanced Environmental Research Institute, Department of Biological Sciences, University of North Texas, Denton, TX 76201, USA;

    Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM 87108, USA;

    Advanced Environmental Research Institute, Department of Biological Sciences, University of North Texas, Denton, TX 76201, USA;

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  • 正文语种 eng
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  • 关键词

    Air pollution; ox-LDL; LOX-1; BBB; Oxidative stress;

    机译：空气污染;ox-LDL;LOX-1;BBB;氧化应激;

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