Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China.
Department of Toxicology, School of Public Health, Hebei Medical University, Shijiazhuang, 050017, China.
Environ Pollut. 2019 May;248:874-887. doi: 10.1016/j.envpol.2019.02.097. Epub 2019 Mar 2.
The development of a rodent ambient particulate matter (PM) inhalation system is critical for drawing causal inferences between PM exposure and the onset of human diseases. In this study, we constructed a real-ambient PM exposure system to investigate multi-organ injury and the reversibility of the impairments in C57BL/6 J male mice exposed to PM with a duration of up to three months in Shijiazhuang, a city with the highest PM2.5 concentration in China. This unique exposure system provided an optimal scenario for round-the-clock PM exposure absent a change in the physiochemical properties of PM and minimized the disturbance to the mice habitat. The mean concentration of PM2.5 in the exposure chambers was 89.95, 79.98, and 87.87 μg/m at three different time points, respectively: weeks 1-3, week 1-6, and week 1-12. The injury in multiple organs, including lung, brain, heart, testis, and intestine, was profound and was evident by the significant pathological and functional alterations. Pulmonary pathological examination revealed severe interstitial inflammatory and alveolar hemorrhage throughout the exposure, which was in line with the reduced lung function and the increased cytokine excretion in bronchoalveolar lavage fluid and blood plasma. Notably, the PM-mediated inflammatory response in different systems was correlated with the severity of the injury and the attenuation of pulmonary lesions in the recovery group. Thus, the PM2.5-induced inflammatory response, the chemical components-induced cytotoxicity, genetic damage, and oxidative stress might be implicated in the impairment of multiple murine organs. These findings revealed the severity, sensitivity, and reversibility of multi-organ injury in response to a real-ambient PM exposure.
构建一种啮齿类动物环境大气颗粒物(PM)吸入系统对于在人类疾病发病前将 PM 暴露与疾病发生之间建立因果关系至关重要。在这项研究中,我们构建了一个真实环境 PM 暴露系统,以研究暴露于 PM 长达三个月的 C57BL/6J 雄性小鼠的多器官损伤及其损伤的可逆性,PM 来源于中国 PM2.5 浓度最高的石家庄市。这种独特的暴露系统为 24 小时不间断的 PM 暴露提供了一个最佳场景,不存在 PM 理化性质的变化,并最大限度地减少了对小鼠栖息地的干扰。暴露室中 PM2.5 的平均浓度在三个不同时间点分别为 89.95、79.98 和 87.87μg/m:第 1-3 周、第 1-6 周和第 1-12 周。肺、脑、心、睾丸和肠等多个器官的损伤非常严重,明显的病理和功能改变表明了这一点。肺部病理学检查显示,整个暴露过程中均存在严重的间质炎症和肺泡出血,这与肺功能下降以及支气管肺泡灌洗液和血浆中细胞因子排泄增加相符。值得注意的是,不同系统中 PM 介导的炎症反应与损伤严重程度以及恢复组中肺部病变的减轻程度相关。因此,PM2.5 诱导的炎症反应、化学物质诱导的细胞毒性、遗传损伤和氧化应激可能与多个小鼠器官的损伤有关。这些发现揭示了真实环境 PM 暴露引起的多器官损伤的严重性、敏感性和可逆性。