Yokota Syunji, Seki Takayuki, Naito Yukiko, Tachibana Shigehiro, Hirabayashi Naoyuki, Nakasaka Toshiaki, Ohara Naoki, Kobayashi Hiroyuki
First Laboratory of Toxicology, Hatano Research Institute, Food and Drug Safety Center, Kanagawa, Japan.
J Toxicol Sci. 2008 Dec;33(5):609-20. doi: 10.2131/jts.33.609.
The influences of inhaling particulate air-pollutants on hematopoiesis and myocardial oxidative stress were investigated in mice by intratracheal instillation (IT) of diesel exhaust particles (DEP), its dichloromethane soluble-component (DMSC) or residual particle-component (RPC). After IT, time courses of cytokine levels in bronchial alveolar lavage fluid (BALF), peripheral blood cell count, myocardial myeloperoxidase (MPO) activity and myocardial chemokine levels were observed for 24 hr. RPC caused sustained blood neutrophilia while that caused by DEP and DMSC was transient. RPC also caused sustained elevations of granulocyte colony-stimulating factor (G-CSF) and interleukin (IL)-6 levels in BALF. Furthermore, IL-1beta level in BALF in the RPC group was significantly elevated at 24 hr after IT. Significant positive correlations were observed between blood neutrophil count and IL-6/G-CSF levels in BALF. MPO activity in the myocardium was increased by RPC at 12 and 24 hr after IT while the activities in the kidney and the liver were not affected. Significant correlation was also observed between myocardial MPO activity and blood neutrophil count at 12 hr after IT, for all three substances. From these results, it was concluded that particle component of DEP may enhance myocardial oxidative stress via blood neutrophilia and the elevation of cytokine levels in BALF.
通过气管内滴注（IT）柴油废气颗粒（DEP）、其二氯甲烷可溶性成分（DMSC）或残留颗粒成分（RPC），研究吸入颗粒空气污染物对小鼠造血和心肌氧化应激的影响。IT后，观察支气管肺泡灌洗液（BALF）中细胞因子水平、外周血细胞计数、心肌髓过氧化物酶（MPO）活性和心肌趋化因子水平的时间进程，持续24小时。RPC导致持续的血液嗜中性粒细胞增多，而DEP和DMSC引起的嗜中性粒细胞增多是短暂的。RPC还导致BALF中粒细胞集落刺激因子（G-CSF）和白细胞介素（IL）-6水平持续升高。此外，RPC组BALF中的IL-1β水平在IT后24小时显著升高。血液嗜中性粒细胞计数与BALF中的IL-6/G-CSF水平之间存在显著正相关。IT后12小时和24小时，RPC使心肌中的MPO活性增加，但肾脏和肝脏中的活性未受影响。对于所有三种物质，IT后12小时心肌MPO活性与血液嗜中性粒细胞计数之间也存在显著相关性。从这些结果得出结论，DEP的颗粒成分可能通过血液嗜中性粒细胞增多和BALF中细胞因子水平升高来增强心肌氧化应激。
