Chronic diesel exhaust exposures of rats demonstrate concentration and time-dependent effects on pulmonary inflammation
Chronic diesel exhaust exposures of rats demonstrate concentration and time-dependent effects on pulmonary inflammation
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DOI：
10.1080/08958370304464
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发表时间：
2003-04-15
影响因子：
2.1
通讯作者：
Kagawa, J
中科院分区：
文献类型：
--
作者：
Ishihara, Y;Kagawa, J
长期反复暴露于空气污染中的颗粒物会增加慢性呼吸道疾病和心肺死亡率的风险。在长期接触颗粒物质方面，对生物联系仍然知之甚少。为了阐明和验证这些联系，我们研究了长期暴露于柴油排放的剂量依赖性和影响的成分没有颗粒柴油排放在大鼠。将Wistar大鼠暴露于过滤空气（C组）、低浓度（L组）、中浓度（M组）、高浓度（H组）柴油机尾气和中等浓度无颗粒物柴油机尾气（MG组）中，16 h/d，6 d/wk，6、12、18或24 mo。处死麻醉动物，并收集肺支气管肺泡灌洗液（BAL）和右心室血液。测定了炎症的各种生物标志物以及粘液和表面活性剂的组分。在实验期间，C、L、M和H组之间的总细胞计数和细胞分化、总蛋白、粘液和表面活性剂组分以及BAL液中的前列腺素E2的变化（而非血浆中的生物标志物）显示出统计学差异。在实验期间，H组的这些生物标志物的变化大于M组，而L组的这些生物标志物与C组相比没有显着变化。M组和H组BAL液中炎性细胞和这些生物标志物的显著变化发生在暴露6至12个月时。暴露12 ~ 18个月时达到最高水平。虽然M和H组暴露6个月时BAL前列腺素E-2显著降低，但在C和L组中未观察到该趋势。在实验期间，暴露于中等水平无颗粒物柴油机废气的动物显示出比暴露于相同水平含颗粒物柴油机废气的动物显著更少的炎性细胞和BAL液中的各种生物标志物。这些结果表明，生物学反应的吸入颗粒物在慢性暴露于柴油机排气剂量依赖性加剧。在24个月的实验期内，炎症和粘液和表面活性剂成分的过度产生在12或18个月的暴露达到一个平台。在这些大鼠中未观察到颗粒（小于1.0 mg颗粒/m3柴油排放）的不良影响。然而，我们的数据表明，颗粒物在柴油机排放废气引起的慢性肺损伤的发展过程中起着重要的作用。
Long-term, repeated exposure to particles in air pollution increases the risk for chronic respiratory diseases and cardiorespiratory mortality. The biological linkages remain poorly understood in chronic exposure to particle matter. To elucidate and verify these linkages, we investigated long-term exposure to diesel emission with respect to dose dependence and the effect of components without particles from diesel emission in rats. Wistar rats were exposed to filtered air (C group), diesel exhaust at low (L group), medium (M group), and high level (H group), or at a medium concentration diesel exhaust without particulate matter (MG group), for 16 h/day, 6 days/wk, for 6, 12, 18, or 24 mo. Anesthetized animals were sacrificed and bronchoalveolar lavage (BAL) fluid from the lung and blood from the right ventricle were collected. Various biomarkers of inflammation and components of mucus and surfactant were determined. Changes in total cell counts and cell differentiation, total protein, mucus and surfactant components, and prostaglandin E 2 in BAL fluid, but not biomarkers in plasma, showed statistical differences among the C, L, M, and H groups during the experimental period. The changes in these biomarkers in the H group were greater than those in the M group, whereas those in the L group showed no significant changes compared with those in the C group during the experimental period. The onset of significant changes in inflammatory cells and these biomarkers in BAL fluid for the M and H groups was at 6 to 12 mo of exposure. The maximum level was reached at 12 to 18 mo of exposure. Although BAL prostaglandin E-2 decreased significantly at 6 mo of exposure in the M and H groups, this trend was not observed in the C and L groups. Animals exposed to a medium level of diesel exhaust without particulate matter showed significantly less inflammatory cells and various biomarkers in BAL fluid than animals exposed to the same level of diesel exhaust with particulate matter during the experimental period. These findings suggest that biological response to inhaled particles is aggravated during chronic exposure to diesel exhaust dose-dependently. Inflammation and overproduction of mucus and surfactant components reached a plateau at 12 or 18 mo of exposure during a 24-mo experimental period. No adverse effect of particles (less than 1.0 mg particles/m(3) of diesel emission) was observed in these rats. However, our data suggest that particulate matter plays an important role during development of chronic lung injury induced by diesel emission exhaust.