Centre of Cardiovascular Science, University of Edinburgh, Edinburgh, Scotland, UK.
Part Fibre Toxicol. 2012 Apr 5;9:9. doi: 10.1186/1743-8977-9-9.
Inhalation of diesel exhaust impairs vascular function in man, by a mechanism that has yet to be fully established. We hypothesised that pulmonary exposure to diesel exhaust particles (DEP) would cause endothelial dysfunction in rats as a consequence of pulmonary and systemic inflammation.
Wistar rats were exposed to DEP (0.5 mg) or saline vehicle by intratracheal instillation and hind-limb blood flow, blood pressure and heart rate were monitored in situ 6 or 24 h after exposure. Vascular function was tested by administration of the endothelium-dependent vasodilator acetylcholine (ACh) and the endothelium-independent vasodilator sodium nitroprusside (SNP) in vivo and ex vivo in isolated rings of thoracic aorta, femoral and mesenteric artery from DEP exposed rats. Bronchoalveolar lavage fluid (BALF) and blood plasma were collected to assess pulmonary (cell differentials, protein levels & interleukin-6 (IL-6)) and systemic (IL-6), tumour necrosis factor alpha (TNFα) and C-reactive protein (CRP)) inflammation, respectively.
DEP instillation increased cell counts, total protein and IL-6 in BALF 6 h after exposure, while levels of IL-6 and TNFα were only raised in blood 24 h after DEP exposure. DEP had no effect on the increased hind-limb blood flow induced by ACh in vivo at 6 or 24 h. However, responses to SNP were impaired at both time points. In contrast, ex vivo responses to ACh and SNP were unaltered in arteries isolated from rats exposed to DEP.
Exposure of rats to DEP induces both pulmonary and systemic inflammation, but does not modify endothelium-dependent vasodilatation. Other mechanisms in vivo limit dilator responses to SNP and these require further investigation.
吸入柴油机废气会损害人体的血管功能，但其机制尚未完全确定。我们假设，由于肺部和全身炎症，肺部接触柴油机废气颗粒（DEP）会导致大鼠的内皮功能障碍。
Wistar 大鼠通过气管内滴注暴露于 DEP（0.5mg）或生理盐水载体，暴露后 6 或 24 小时在原位监测后肢血流、血压和心率。通过给予内皮依赖性血管扩张剂乙酰胆碱（ACh）和内皮非依赖性血管扩张剂硝普钠（SNP），在体内和体外测试DEP 暴露大鼠的血管功能，分别在胸主动脉、股动脉和肠系膜动脉的分离环中进行。收集支气管肺泡灌洗液（BALF）和血浆，以评估肺部（细胞差异、蛋白水平和白细胞介素 6（IL-6））和全身（IL-6、肿瘤坏死因子α（TNFα）和 C 反应蛋白（CRP））炎症。
DEP 滴注后 6 小时，BALF 中的细胞计数、总蛋白和 IL-6 增加，而 DEP 暴露后 24 小时仅在血液中升高 IL-6 和 TNFα 水平。DEP 对 ACh 在体内引起的后肢血流增加没有影响，但在 6 或 24 小时时均会损害对 SNP 的反应。相比之下，DEP 暴露大鼠分离的动脉中，ACh 和 SNP 的体外反应未改变。
大鼠暴露于 DEP 会引起肺部和全身炎症，但不会改变内皮依赖性血管舒张。体内其他机制限制了对 SNP 的扩张反应，这需要进一步研究。
