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大鼠肺中的氧化应激与核因子κB激活:煤烟与铁颗粒之间的协同相互作用

Oxidative stress and NFkappaB activation in the lungs of rats: a synergistic interaction between soot and iron particles.

作者信息

Zhou Ya-Mei, Zhong Cai-Yun, Kennedy Ian M, Leppert Valerie J, Pinkerton Kent E

机构信息

Center for Health and the Environment, Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.

出版信息

Toxicol Appl Pharmacol. 2003 Jul 15;190(2):157-69. doi: 10.1016/s0041-008x(03)00157-1.

Abstract

Particulate matter (PM) has been associated with a variety of adverse health effects primarily involving the cardiopulmonary system. However, the precise biological mechanisms to explain how exposure to PM exacerbates or directly causes adverse effects are unknown. Particles of varying composition may play a critical role in these effects. To study such a phenomenon, a simple, laminar diffusion flame was used to generate aerosols of soot and iron particles in the ultrafine size range. Exposures of healthy adult rats were for 6 h/day for 3 days. Conditions used included exposure to soot only, iron only, or a combination of soot and iron. We found animals exposed to soot particles at 250 microg/m3 had no adverse respiratory effects. Exposure to iron alone at a concentration of 57 microg/m3 also had no respiratory effects. However, the addition of 45 microg/m3 of iron to soot with a combined total mass concentration of 250 microg/m3 demonstrated significant pulmonary ferritin induction, oxidative stress, elevation of IL-1beta, and cytochrome P450s, as well as activation of NFkappaB. These findings suggest that a synergistic interaction between soot and iron particles account for biological responses not found with exposure to iron alone or to soot alone.

摘要

颗粒物(PM)已被证实与多种主要涉及心肺系统的不良健康影响相关。然而,关于暴露于PM如何加剧或直接导致不良反应的精确生物学机制尚不清楚。不同成分的颗粒可能在这些影响中起关键作用。为了研究这种现象,我们使用了一种简单的层流扩散火焰来生成超细尺寸范围内的烟灰和铁颗粒气溶胶。对健康成年大鼠进行为期3天、每天6小时的暴露实验。实验条件包括仅暴露于烟灰、仅暴露于铁或同时暴露于烟灰和铁。我们发现,暴露于浓度为250微克/立方米的烟灰颗粒的动物没有出现不良呼吸影响。暴露于浓度为57微克/立方米的铁也没有产生呼吸影响。然而,在总质量浓度为250微克/立方米的烟灰中添加45微克/立方米的铁后,出现了显著的肺铁蛋白诱导、氧化应激、白细胞介素-1β升高、细胞色素P450s以及核因子κB激活。这些发现表明,烟灰和铁颗粒之间的协同相互作用导致了单独暴露于铁或单独暴露于烟灰时未出现的生物学反应。

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