Mechanisms of particulate matter toxicity in neonatal and young adult rat lungs.
Mechanisms of particulate matter toxicity in neonatal and young adult rat lungs.
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发表时间：
2008-10
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通讯作者：
K. Pinkerton;Yamei Zhou;C. Zhong;Kevin R. Smith;S. Teague;I. Kennedy;M. Ménache
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作者：
K. Pinkerton;Yamei Zhou;C. Zhong;Kevin R. Smith;S. Teague;I. Kennedy;M. Ménache
颗粒物 (PM*) 与多种不良健康影响有关，主要涉及心血管和呼吸系统。研究人员继续研究可能解释 PM 暴露如何加剧或直接导致不良影响的生物学机制。颗粒成分可能在这些效应中发挥关键作用。在这项研究中，我们使用扩散火焰系统来产生超细铁、烟灰和铁与烟灰颗粒的结合，并将年轻成年和新生大鼠暴露于这些颗粒的不同成分中。年轻成年大鼠连续三天吸入所有三种 PM 组合物，每天 6 小时。暴露于 250 微克/立方米的烟尘 PM 或 57 微克/立方米的铁 PM 中，没有表现出不良的呼吸影响。然而，当铁浓度增加至 90 微克/立方米时，我们观察到轻微的肺应激。当老鼠吸入由铁（45微克/立方米）和烟灰颗粒（总质量250微克/立方米）组成的PM时，产生最显着的效果。这种类型的暴露会产生显着的氧化应激指标、炎症迹象以及肺部细胞色素 P450 同工酶水平的增加。在生命的第二周和第四周，新生大鼠反复接触烟灰和铁颗粒三天，会产生显着的氧化应激（氧化和还原型谷胱甘肽升高）和铁蛋白诱导。在生命第二周暴露于 PM 的新生大鼠的肺部中央区域的细胞增殖也出现了微妙但显着的减少。这些发现表明，铁与烟尘 PM 结合可导致呼吸道发生变化，而这种变化是单独接触类似浓度的铁或烟尘 PM 时未发现的。对新生儿的独特影响表明，年龄可能在对吸入颗粒的易感性中发挥重要作用。
Particulate matter (PM*) has been associated with a variety of adverse health effects, primarily involving the cardiovascular and respiratory systems. Researchers continue to investigate biologic mechanisms that may explain how exposure to PM exacerbates or directly causes adverse effects. Particle composition may play a critical role in these effects. In this study we used a diffusion flame system to generate ultrafine iron, soot, and iron combined with soot particles and exposed young adult and neonatal rats to different compositions of these particles. Young adult rats inhaled all three PM compositions on three consecutive days for 6 hours per day. Exposure to soot PM at 250 microg/m3 or to iron PM at 57 microg/m3 demonstrated no adverse respiratory effects. However, we observed mild pulmonary stress when the iron concentration was increased to 90 microg/m3. The most striking effects resulted when the rats inhaled PM composed of iron (45 microg/m3) combined with soot particles (total mass 250 microg/m3). This type of exposure produced significant indicators of oxidative stress, signs of inflammation, and increases in the levels of cytochrome P450 isozymes in the lungs. Repeated three-day exposure of neonatal rats to soot and iron particles in the second and the fourth weeks of life produced significant oxidative stress (elevations in oxidized and reduced glutathione) and ferritin induction. Neonatal rats exposed to PM in the second week of life also had a subtle but significant cell proliferation reduction in the centriacinar regions of the lungs. These findings suggest that iron combined with soot PM can lead to changes in the respiratory tract not found with exposure to iron or soot PM alone at similar concentrations. Unique effects in the neonate suggest that age may play an important role in susceptibility to inhaled particles.