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棕色挪威大鼠急性和亚慢性间歇性臭氧暴露对肺部影响的年龄相关差异。

Age-related differences in pulmonary effects of acute and subchronic episodic ozone exposures in Brown Norway rats.

作者信息

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

机构信息

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.

出版信息

Inhal Toxicol. 2016 Jun;28(7):313-23. doi: 10.3109/08958378.2016.1170910. Epub 2016 Apr 21.

Abstract

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.

摘要

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。

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