Distal airway remodeling in rats chronically exposed to ozone.
Distal airway remodeling in rats chronically exposed to ozone.
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DOI：
10.1164/ajrccm/137.4.924
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发表时间：
1988-04
期刊：
影响因子：
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通讯作者：
B. C. Barr;D. Hyde;C. Plopper;D. Dungworth
中科院分区：
文献类型：
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作者：
B. C. Barr;D. Hyde;C. Plopper;D. Dungworth
对14只大鼠暴露于过滤空气（8）或0.95ppm臭氧（6）中，每天8小时，持续90天，从形态学和形态计量学上检查肺腺泡中心区的形态变化。通过腹膜内给予过量戊巴比妥钠处死大鼠，气管插管，并从胸部取出胸腔脏器和肺。在30 cm水压下，通过气管内滴注多聚甲醛/戊二醛二甲胂酸盐缓冲固定剂固定肺。通过重量位移确定肺体积，并将左肺叶横向切片成12个厚片。取脑叶头侧、中部和尾侧三分之一的三块厚片，用石蜡包埋，并进行光学显微镜研究。通过这些切片，我们估计了肺内近端细支气管、终末细支气管、呼吸性细支气管和联合肺泡管/囊的体积。通过透射电子显微镜研究了从右中叶预选区域解剖的细支气管。在纵向平面上通过中腔切开终末气道。从这些解剖的气道，然后检查了中心腺泡的4个亚区：（1）终末细支气管，（2）呼吸性细支气管，（3）中心腺泡肺泡管壁，（4）中心腺泡肺泡隔。本研究结果显示，慢性臭氧暴露后，终末细支气管管腔直径减少13%至21%，但终末细支气管总体积无显著变化。最显著的变化是呼吸性细支气管容积增加了3.4倍。终末细支气管的测量体积和直径变化的分析，加上呼吸性细支气管的体积增加，支持呼吸性细支气管（RB）是从中央腺泡肺泡管形成的结论。支持这一结论的形态学参数包括RB中反应性细支气管上皮下存在融合的基底膜，RB和近端肺泡管间隔尖端存在类似的基底层变化，以及观察到最严重的上皮损伤和炎症发生在最近端肺泡管而不是终末细支气管。本研究的一个主要结论是，随着呼吸性细支气管段的形成，腺泡内最严重损伤的焦点似乎向远端转移。因此，大多数损伤发生在呼吸性细支气管肺泡管连接处的肺泡隔尖端。
The morphologic changes in the centriacinar region of lungs from 14 rats exposed to either filtered air (8) or 0.95 ppm ozone (6) 8 hours daily for 90 days were examined morphologically and morphometrically. Rats were killed with an overdose of sodium pentobarbital administered intraperitoneally, the trachea cannulated, and thoracic viscera and lungs removed from the chest. Lungs were fixed via intratracheal instillation of a paraformaldehyde/glutaraldehyde cacodylate buffered fixative at 30 cm water pressure. Lung volumes were determined by weight displacement and the left lung lobe was sectioned transversely into 12 slabs. Three slabs from the cranial, middle, and caudal thirds of the lobe were embedded in paraffin and studied by light microscopy. With these sections, we estimated the volume of proximal bronchiole, terminal bronchiole, respiratory bronchiole, and combined alveolar duct/sac within the lung. Bronchioles dissected from preselected regions of the right middle lobe were studied by transmission electron microscopy. Dissected terminal airways were sectioned in a longitudinal plane through their midlumen. From these dissected airways, 4 subregions of the centriacinus were then examined: (1) terminal bronchiole, (2) respiratory bronchiole, (3) centriacinar alveolar duct wall, and (4) centriacinar alveolar septa. The results of this study showed that after chronic ozone exposure, there was a 13 to 21% decrease in terminal bronchiole luminal diameter but no significant change in total terminal bronchiole volume. The most notable change was a 3.4-fold increase in respiratory bronchiole volume. Analysis of measured volume and diameter changes in the terminal bronchiole, coupled with volume increases in respiratory bronchiole, support the conclusion that respiratory bronchiole (RB) is formed from the centriacinar alveolar duct. Morphologic parameters supporting this conclusion included the presence of fused basement membrane beneath reactive bronchiolar epithelium in the RB, the presence of similar basal laminar changes in both the RB and proximal alveolar duct septal tips, and the observation that most severe epithelial damage and inflammation occurred in the most proximal alveolar duct rather than in the terminal bronchiole. A major conclusion of this study is that the focus of the most severe injury within the acinus appears to shift distally as respiratory bronchiole segments are formed. Hence most of the damage occurs at the tips of alveolar septa at the respiratory bronchiole-alveolar duct junction.