Inoue Ken-ichiro, Takano Hirohisa, Yanagisawa Rie, Ichinose Takamichi, Sadakane Kaori, Yoshino Shin, Yamaki Kouya, Uchiyama Kazuhiko, Yoshikawa Toshikazu
Inhalation Toxicology and Pathophysiology Research Team, National Institute for Environmental Studies, Ibaraki, Japan.
J Appl Toxicol. 2004 Nov-Dec;24(6):415-8. doi: 10.1002/jat.984.
We have reported previously that components of diesel exhaust particles (DEP) differently affect acute lung injury related to lipopolysaccharide (LPS) in mice. This study examined the effects of components of DEP on the lung expression of cyclooxygenase (COX)-1 and -2 in the presence or absence of LPS. ICR mice were divided into six experimental groups that received vehicle, LPS (2.5 mg kg(-1)), organic chemicals in DEP (DEP-OC) extracted with dichloromethane (4 mg kg(-1)), residual carbonaceous nuclei after the extraction (washed DEP: 4 mg kg(-1)), DEP-OC (4 mg kg(-1)) + LPS (2.5 mg kg(-1)) or washed DEP (4 mg kg(-1)) + LPS (2.5 mg kg(-1)) intratracheally. The expression of mRNA for both COXs in the lung was evaluated 4 h after the intratracheal administration. The magnitude of COX-1 mRNA expression was not altered in each group. The LPS treatment enhanced the COX-2 gene expression compared with vehicle treatment. Washed DEP combined with LPS further increased its expression compared with LPS alone. In contrast, combined treatment of DEP-OC with LPS decreased COX-2 gene expression compared with LPS alone. These results suggest that the residual carbonaceous nuclei of DEP predominantly enhance lung expression of COX-2 rather than the extracted organic chemicals from DEP in the presence of LPS, which is concomitant with the magnitude of acute lung injury in our previous study.
我们之前曾报道过，柴油尾气颗粒（DEP）的成分对小鼠中与脂多糖（LPS）相关的急性肺损伤有不同影响。本研究检测了在有或无LPS存在的情况下，DEP成分对肺中环氧合酶（COX）-1和-2表达的影响。将ICR小鼠分为六个实验组，分别气管内给予赋形剂、LPS（2.5 mg kg⁻¹）、用二氯甲烷提取的DEP中的有机化学物质（DEP-OC：4 mg kg⁻¹）、提取后的残留碳质核（洗涤后的DEP：4 mg kg⁻¹）、DEP-OC（4 mg kg⁻¹）+LPS（2.5 mg kg⁻¹）或洗涤后的DEP（4 mg kg⁻¹）+LPS（2.5 mg kg⁻¹）。气管内给药4小时后评估肺中两种COX的mRNA表达。每组中COX-1 mRNA表达的幅度没有改变。与赋形剂处理相比，LPS处理增强了COX-2基因表达。与单独使用LPS相比，洗涤后的DEP与LPS联合使用进一步增加了其表达。相反，与单独使用LPS相比，DEP-OC与LPS联合处理降低了COX-2基因表达。这些结果表明，在LPS存在的情况下，DEP的残留碳质核对COX-2肺表达的增强作用主要而非从DEP中提取的有机化学物质，这与我们之前研究中急性肺损伤的程度一致。
