Department of Occupational and Environmental Health Sciences, School of Public Health, Peking University, Beijing 100191, PR China.
Toxicol Lett. 2013 Nov 25;223(2):146-53. doi: 10.1016/j.toxlet.2013.09.004. Epub 2013 Sep 14.
Air pollution is associated with significant adverse health effects including increased cardiovascular morbidity and mortality. However research on the cardiovascular effect of "real-world" exposure to ambient particulate matter (PM) in susceptible animal model is very limited. In this study, we aimed to investigate the association between Beijing ambient particle exposure and the atherosclerosis development in the apolipoprotein E knockout mice (ApoE(-/-) mice).
Two parallel exposure chambers were used for whole body exposure among ApoE knockout mice. One of the chambers was supplied with untreated ambient air (PM group) and the other chamber was treated with ambient air filtered by high-efficiency particulate air (HEPA) filter (FA group). Twenty mice were divided into two groups and exposed to ambient PM (n=10 for PM group) or filtered air (n=10 for FA group) for two months from January 18th to March 18th, 2010. During the exposure, the mass concentrations of PM2.5 and PM10 in the two chambers were continuously monitored. Additionally, a receptor source apportionment model of chemical mass balance using 19 organic tracers was applied to determine the contributions of sources on the PM2.5 in terms of natural gas, diesel vehicle, gasoline vehicle, coal burning, vegetable debris, biomass burning and cooking. At the end of the two-month exposure, biomarkers of oxidative stress, inflammation and lipid metabolism in bronchoalveolar lavage fluid (BAL) and blood samples were determined and the plaque area on the aortic endothelium was quantified.
In the experiment, the concentrations of PM10 and PM2.5 in PM chamber were 99.45μg/m(3) and 61.0μg/m(3) respectively, while PM2.5 in FA chamber was 17.6μg/m(3). Source apportionment analysis by organic tracers showed that gasoline vehicle (39.9%) and coal burning (24.3%) emission were the two major sources contributing to the mass concentration of PM2.5 in Beijing. Among the ApoE knockout mice, the PM group were significantly higher than the FA group in terms of serum total cholesterol, low-density lipoprotein, tumor necrosis factor-alpha (TNF-alpha) and C-reactive protein as well as TNF-alpha and interleukin-6 in BAL. Also the total antioxidant capacity and oxidized low-density lipoprotein were significantly different between the two groups. In addition, pathological analysis of aortic arch reveals that the plaques area in the PM group increased significantly compared to the FA group.
Our results demonstrated that ambient PM exposure could induce considerable oxidative stress and systemic inflammation in ApoE knockout mice and contribute to the progression of atherosclerosis.
空气污染与显著的不良健康影响有关，包括心血管发病率和死亡率的增加。然而，在易感动物模型中，关于“真实世界”环境颗粒物（PM）暴露的心血管效应的研究非常有限。在这项研究中，我们旨在研究北京大气颗粒物暴露与载脂蛋白 E 基因敲除（ApoE(-/-)）小鼠动脉粥样硬化发展之间的关系。
使用两个平行的全身暴露室对 ApoE 基因敲除小鼠进行全身暴露。其中一个室供应未处理的大气颗粒物（PM 组），另一个室供应高效空气过滤器（HEPA）过滤的空气（FA 组）。20 只小鼠被分为两组，分别在 2010 年 1 月 18 日至 3 月 18 日期间暴露于大气 PM（n=10，PM 组）或过滤空气（n=10，FA 组）两个月。暴露期间，连续监测两个室内的 PM2.5 和 PM10 质量浓度。此外，应用基于化学质量平衡的受体源分配模型，利用 19 种有机示踪剂确定天然气、柴油车、汽油车、燃煤、植物碎屑、生物质燃烧和烹饪等来源对 PM2.5 的贡献。在为期两个月的暴露结束时，测定支气管肺泡灌洗液（BAL）和血液样本中的氧化应激、炎症和脂质代谢生物标志物，并定量主动脉内皮上的斑块面积。
在实验中，PM 室中的 PM10 和 PM2.5 浓度分别为 99.45μg/m3 和 61.0μg/m3，而 FA 室中的 PM2.5 浓度为 17.6μg/m3。通过有机示踪剂进行的源分配分析表明，汽油车（39.9%）和燃煤（24.3%）排放是导致北京 PM2.5 质量浓度的两个主要来源。在 ApoE 基因敲除小鼠中，PM 组的血清总胆固醇、低密度脂蛋白、肿瘤坏死因子-α（TNF-α）和 C 反应蛋白以及 BAL 中的 TNF-α和白细胞介素-6明显高于 FA 组。此外，两组之间的总抗氧化能力和氧化型低密度脂蛋白也有明显差异。此外，主动脉弓的病理分析表明，与 FA 组相比，PM 组的斑块面积显著增加。
我们的结果表明，大气颗粒物暴露可导致 ApoE 基因敲除小鼠产生相当大的氧化应激和全身炎症，并促进动脉粥样硬化的发展。
