全氟异丁烯暴露致急性肺损伤时血-气屏障的细胞损伤。

Cell injuries of the blood-air barrier in acute lung injury caused by perfluoroisobutylene exposure.

机构信息

Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, PR China.

出版信息

J Occup Health. 2010;52(1):48-57. doi: 10.1539/joh.l9047. Epub 2009 Dec 25.

DOI:10.1539/joh.l9047

PMID:20035103

Abstract

OBJECTIVES

To investigate the complete process of cell injuries in the blood-air barrier after perfluoroisobutylene (PFIB) exposure.

METHODS

Rats were exposed to PFIB (140 mg/m(3)) for 5 min. The pathological changes were evaluated by lung wet-to-dry weight ratio, total protein concentration of bronchoalveolar lavage fluid and HE stain. Ultrastructural changes were observed by transmission electron microscope. Apoptosis was detected by in situ apoptosis detection. Changes of actin in the lung tissue were evaluated by western blot assay.

RESULTS

No significant pulmonary edema or increased permeability was observed within the first 4 h, post PFIB exposure. However, inflammatory cell infiltration and alveolar wall thickening were observed from 2 h. Destruction of the alveoli constitution integrity, edema and protein leakage were observed at 8 h. The injuries culminated at 24 h and then recovered gradually. The ultrastructural injuries of alveolar type I epithelial cells, alveolar type II epithelial cells and pulmonary microvascular endothelial cells were observed at 30 min post PFIB exposure. Some injuries were similar to apoptosis. Compared with control, more serious injuries were observed in PFIB-exposed rats after 30 min. At 8 h, some signs of cell necrosis were observed. The injuries culminated at 24 h and then ameliorated. The number of apoptotic cells abnormally increased at 30 min post PFIB exposure, the maximum appeared at 24 h, and then ameliorated gradually. Western blot analysis revealed that the level of actin in the lung showed no significant changes within the first 4 h post PFIB exposure. However, it decreased at 8 h, reached a nadir at 24 h, and then recovered gradually.

CONCLUSIONS

The pathological processes were in progress persistently post PFIB exposure. The early injuries probably were the result of the direct attack of PFIB and the advanced injuries probably arose from the inflammatory reaction induced by PFIB.

摘要

目的

研究全氟异丁烯（PFIB）暴露后血-气屏障细胞损伤的全过程。

方法

将大鼠暴露于 PFIB（140mg/m³）中 5 分钟。通过肺湿重/干重比、支气管肺泡灌洗液总蛋白浓度和 HE 染色评估病理变化。通过透射电镜观察超微结构变化。通过原位凋亡检测检测细胞凋亡。通过 Western blot 分析评估肺组织中肌动蛋白的变化。

结果

PFIB 暴露后 4 小时内，未见明显肺水肿或通透性增加。然而，在 2 小时时观察到炎性细胞浸润和肺泡壁增厚。在 8 小时时观察到肺泡结构完整性破坏、水肿和蛋白渗漏。损伤在 24 小时达到高峰，然后逐渐恢复。在 PFIB 暴露后 30 分钟即可观察到肺泡 I 型上皮细胞、肺泡 II 型上皮细胞和肺微血管内皮细胞的超微结构损伤，有些损伤类似于细胞凋亡。与对照组相比，PFIB 暴露后 30 分钟大鼠的损伤更严重。在 8 小时时，观察到一些细胞坏死的迹象。损伤在 24 小时达到高峰，然后逐渐缓解。PFIB 暴露后 30 分钟，异常凋亡细胞数量增加，24 小时达到最大值，然后逐渐恢复。Western blot 分析显示，PFIB 暴露后 4 小时内肺内肌动蛋白水平无明显变化。然而，在 8 小时时下降，在 24 小时时达到最低点，然后逐渐恢复。