Department of Physiology, Faculty of Medicine and Health Sciences, United Arab Emirates University, Al Ain, Abu Dhabi, United Arab Emirates.
Toxicol Lett. 2010 May 4;194(3):58-65. doi: 10.1016/j.toxlet.2010.02.001. Epub 2010 Feb 8.
Nanosized fraction of particulate air pollution has been reported to translocate from the airways into the bloodstream and act on different organs. However, the direct effect of these translocated particles is not well understood. In this study, we determined the time-course (6 h, 18 h, 48 h and 168 h) effects of the systemic administration of 0.02 mg/kg diesel exhaust particles (DEP) on systolic blood pressure (SBP), systemic inflammation, oxidative status, and morphological alterations in lungs, heart, liver and kidneys in Wistar rats. SBP was significantly decreased at 6 h (P < 0.05) but no significant effects have been observed at later time points. The leukocyte numbers were increased at 6 h (P < 0.05) and 18 h (P < 0.05). However, the platelet numbers were significantly decreased (P < 0.05) 6 h following the systemic administration of DEP. The IL-6 concentrations in plasma was increased at 6 h (P < 0.05) and 18 h (P < 0.05). Similarly, superoxide dismutase activity was significantly increased at 6 (P = 0.01) and 18 h (P < 0.05) following DEP exposure. The direct addition of DEP (0.1-1 microg/ml) to untreated rat blood significantly induced in vitro platelet aggregation in a dose-dependent fashion. The activation of intravascular coagulation was confirmed by a dose-dependent shortening of activated partial thromboplastin time and the prothrombin time following in vitro exposure to DEP (0.25-1 microg/ml). Histological analysis revealed the presence of DEP in the lungs, heart, liver and kidneys. However, the morphological changes were only observed in the lungs, where the presence of infiltration of inflammatory cells was observed as early as 6 h, increased at 18 h, and decreased in intensity at 48 h and at 168 h. We conclude that the direct systemic administration of DEP caused acute effect on SBP (6 h) and systemic inflammation and oxidative stress mainly at 6 h and 18 h. Despite the presence of DEP in lungs, heart, liver and kidneys, the histopathological changes were only seen in the lung which suggests that, at the dose and time-points investigated, DEP cause inflammation and have a predilection for pulmonary tissue.
纳米级的颗粒物已经被报道可以从气道转移到血液中，并作用于不同的器官。然而，这些转移颗粒的直接作用尚不清楚。在这项研究中，我们测定了系统性给予 0.02 毫克/千克柴油废气颗粒（DEP）后 6 小时、18 小时、48 小时和 168 小时对 Wistar 大鼠的收缩压（SBP）、全身炎症、氧化状态以及肺、心、肝和肾的形态改变的时间过程（6 h、18 h、48 h 和 168 h）的影响。SBP 在 6 小时（P < 0.05）显著降低，但在以后的时间点没有观察到显著影响。白细胞数量在 6 小时（P < 0.05）和 18 小时（P < 0.05）增加。然而，血小板数量在给予 DEP 后 6 小时（P < 0.05）显著降低。血浆中 IL-6 浓度在 6 小时（P < 0.05）和 18 小时（P < 0.05）增加。同样，超氧化物歧化酶活性在 DEP 暴露后 6 小时（P = 0.01）和 18 小时（P < 0.05）显著增加。DEP（0.1-1 微克/毫升）直接加入未经处理的大鼠血液中，以剂量依赖性方式显著诱导体外血小板聚集。体外暴露于 DEP（0.25-1 微克/毫升）后，激活部分凝血活酶时间和凝血酶原时间的剂量依赖性缩短证实了血管内凝血的激活。组织学分析显示 DEP 存在于肺、心、肝和肾中。然而，形态学变化仅在肺中观察到，在 6 小时时观察到炎症细胞浸润，在 18 小时时增加，在 48 小时和 168 小时时减少。我们得出结论，直接给予 DEP 会导致 SBP（6 小时）和全身炎症和氧化应激的急性影响，主要发生在 6 小时和 18 小时。尽管 DEP 存在于肺、心、肝和肾中，但仅在肺中观察到组织病理学变化，这表明在研究的剂量和时间点，DEP 引起炎症，并对肺组织有偏好。
