Snow Samantha J, Gordon Christopher J, Bass Virginia L, Schladweiler Mette C, Ledbetter Allen D, Jarema Kimberly A, Phillips Pamela M, Johnstone Andrew F, Kodavanti Urmila P
a Environmental Public Health Division and NHEERL, US Environmental Protection Agency, Research Triangle Park , NC , USA .
b Toxicity Assessment Division, NHEERL, US Environmental Protection Agency, Research Triangle Park , NC , USA , and.
Inhal Toxicol. 2016 Jun;28(7):313-23. doi: 10.3109/08958378.2016.1170910. Epub 2016 Apr 21.
Ozone (O3) is known to induce adverse pulmonary and systemic health effects. Importantly, children and older persons are considered at-risk populations for O3-induced dysfunction, yet the mechanisms accounting for the age-related pulmonary responses to O3 are uncertain. In this study, we examined age-related susceptibility to O3 using 1 mo (adolescent), 4 mo (young adult), 12 mo (adult) and 24 mo (senescent) male Brown Norway rats exposed to filtered air or O3 (0.25 and 1.00 ppm), 6 h/day, two days/week for 1 week (acute) or 13 weeks (subchronic). Ventilatory function, assessed by whole-body plethysmography, and bronchoalveolar lavage fluid (BALF) biomarkers of injury and inflammation were used to examine O3-induced pulmonary effects. Relaxation time declined in all ages following the weekly exposures; however, this effect persisted only in the 24 mo rats following a five days recovery, demonstrating an inability to induce adaptation commonly seen with repeated O3 exposures. PenH was increased in all groups with an augmented response in the 4 mo rats following the subchronic O3 exposures. O3 led to increased breathing frequency and minute volume in the 1 and 4 mo animals. Markers of pulmonary permeability were increased in all age groups. Elevations in BALF γ-glutamyl transferase activity and lung inflammation following an acute O3 exposure were noted in only the 1 and 4 mo rats, which likely received an increased effective O3 dose. These data demonstrate that adolescent and young adult animals are more susceptible to changes in ventilation and pulmonary injury/inflammation caused by acute and episodic O3 exposure.
已知臭氧(O₃)会对肺部和全身健康产生不良影响。重要的是,儿童和老年人被认为是O₃诱导功能障碍的高危人群,但导致肺部对O₃产生年龄相关反应的机制尚不清楚。在本研究中,我们使用1个月大(青少年)、4个月大(青年)、12个月大(成年)和24个月大(衰老)的雄性挪威棕色大鼠,将其暴露于过滤空气或O₃(0.25和1.00 ppm)中,每天6小时,每周两天,持续1周(急性)或13周(亚慢性),以研究对O₃的年龄相关易感性。通过全身体积描记法评估通气功能,并使用支气管肺泡灌洗液(BALF)中损伤和炎症的生物标志物来检查O₃诱导的肺部效应。每周暴露后,所有年龄段的松弛时间均下降;然而,这种效应仅在恢复五天后的24个月大大鼠中持续存在,表明无法诱导出反复暴露于O₃时常见的适应性。亚慢性O₃暴露后,所有组的PenH均增加,4个月大大鼠的反应增强。O₃导致1个月和4个月大动物的呼吸频率和分钟通气量增加。所有年龄组的肺通透性标志物均增加。仅在1个月和4个月大的大鼠中观察到急性O₃暴露后BALFγ-谷氨酰转移酶活性升高和肺部炎症,这可能是因为它们接受了增加的有效O₃剂量。这些数据表明,青少年和青年动物更容易受到急性和间歇性O₃暴露引起的通气变化以及肺部损伤/炎症的影响。