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模拟月球和火星尘埃对小鼠的肺毒性:I. 气管内滴注后7天和90天的组织病理学

Pulmonary toxicity of simulated lunar and Martian dusts in mice: I. Histopathology 7 and 90 days after intratracheal instillation.

作者信息

Lam Chiu-Wing, James John T, McCluskey Richard, Cowper Shawn, Balis John, Muro-Cacho Carlos

机构信息

Wyle Laboratories, NASA Johnson Space Center, Houston, Texas 77058, USA.

出版信息

Inhal Toxicol. 2002 Sep;14(9):901-16. doi: 10.1080/08958370290084683.

DOI:10.1080/08958370290084683
PMID:12396402
Abstract

NASA is contemplating sending humans to Mars and to the moon for further exploration. Volcanic ashes from Arizona and Hawaii with mineral properties similar to those of lunar and Martian soils, respectively, are used to simulate lunar and Martian environments for instrument testing. Martian soil is highly oxidative; this property is not found in Earth's volcanic ashes. NASA is concerned about the health risk from potential exposure of workers in the test facilities. Fine lunar soil simulant (LSS), Martian soil simulant (MSS), titanium dioxide, or quartz in saline was intratracheally instilled into groups of 4 mice (C57BL/6J) at 0.1 mg/mouse (low dose, LD) or 1 mg/mouse (high dose, HD). Separate groups of mice were exposed to ozone (0.5 ppm for 3 h) prior to MSS instillation. Lungs were harvested for histopathological examination 7 or 90 days after the single dust treatment. The lungs of the LSS-LD groups showed no evidence of inflammation, edema, or fibrosis; clumps of particles and an increased number of macrophages were visible after 7 days but not 90 days. In the LSS-HD-7d group, the lungs showed mild to moderate alveolitis, and perivascular and peribronchiolar inflammation. The LSS-HD-90d group showed signs of mild chronic pulmonary inflammation, septal thickening, and some fibrosis. Foci of particle-laden macrophages (PLMs) were still visible. Lung lesions in the MSS-LD-7d group were similar to those observed in the LSS-HD-7d group. The MSS-LD-90d group had PLMs and scattered foci of mild fibrosis in the lungs. The MSS-HD-7d group showed large foci of PLMs, intra-alveolar debris, mild-to-moderate focal alveolitis, and perivascular and peribronchiolar inflammation. The MSS-HD-90d group showed focal chronic mild-to-moderate alveolitis and fibrosis. The findings in the O(3)-MSS-HD-90d group included widespread intra-alveolar debris, focal moderate alveolitis, and fibrosis. Lung lesions in the MSS groups were more severe with the ozone pretreatment. The effects of O(3) and MSS coexposure appeared to be more than additive. Results for the TiO(2) and quartz controls were consistent with the known pulmonary toxicity of these compounds. The overall severity of lung injury was TiO(2) < LSS < MSS < O(3) + MSS < quartz. Except for TiO(2), the increased duration of dust presence in the lung from 7 to 90 days transformed the acute inflammatory response to a chronic inflammatory lesion. This study showed that LSS and MSS are more hazardous in the lungs than nuisance dusts.

摘要

美国国家航空航天局(NASA)正在考虑将人类送往火星和月球进行进一步探索。分别取自亚利桑那州和夏威夷的具有与月球和火星土壤相似矿物特性的火山灰,被用于模拟月球和火星环境以进行仪器测试。火星土壤具有高度氧化性,而这种特性在地球的火山灰中并未发现。NASA担心测试设施中的工作人员因潜在暴露而面临健康风险。将精细的月球土壤模拟物(LSS)、火星土壤模拟物(MSS)、二氧化钛或石英盐水溶液以每只小鼠0.1毫克(低剂量,LD)或1毫克(高剂量,HD)的剂量经气管内注入4组C57BL/6J小鼠。在注入MSS之前,将单独的几组小鼠暴露于臭氧(0.5 ppm,持续3小时)。在单次粉尘处理后7天或90天采集肺部进行组织病理学检查。LSS - LD组的肺部未显示出炎症、水肿或纤维化的迹象;7天后可见颗粒团块和巨噬细胞数量增加,但90天后未观察到。在LSS - HD - 7d组中,肺部显示轻度至中度肺泡炎以及血管周围和支气管周围炎症。LSS - HD - 90d组显示出轻度慢性肺部炎症、间隔增厚和一些纤维化的迹象。仍可见载有颗粒的巨噬细胞(PLM)灶。MSS - LD - 7d组的肺部病变与LSS - HD - 7d组观察到的相似。MSS - LD - 90d组肺部有PLM和散在的轻度纤维化灶。MSS - HD - 7d组显示大量PLM灶、肺泡内碎片、轻度至中度局灶性肺泡炎以及血管周围和支气管周围炎症。MSS - HD - 90d组显示局灶性慢性轻度至中度肺泡炎和纤维化。O(3) - MSS - HD - 90d组的发现包括广泛的肺泡内碎片、局灶性中度肺泡炎和纤维化。臭氧预处理后,MSS组的肺部病变更严重。臭氧和MSS共同暴露的影响似乎大于相加作用。二氧化钛和石英对照组的结果与这些化合物已知的肺毒性一致。肺损伤的总体严重程度为:二氧化钛<LSS<MSS<臭氧 + MSS<石英。除二氧化钛外,肺部粉尘存在时间从7天延长至90天,将急性炎症反应转变为慢性炎症病变。这项研究表明,LSS和MSS对肺部的危害比普通粉尘更大。

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