Gordon R E, Solano D, Kleinerman J
Exp Lung Res. 1986;11(3):179-93. doi: 10.3109/01902148609064295.
Acute exposure to NO2 is reported to disrupt tight junctions in lung epithelium. We have studied the effects of chronic NO2 exposure and recovery breathing clean air to tight junctions of distal airway and alveolar epithelium. Syrian Golden hamsters were exposed to NO2 (30 PPM) for 5 or 9 months and a group of those animals for 9 months were allowed to recover breathing clean air for 3 or 9 months. Animals were sacrificed after 5 and 9 months of NO2 exposure and after 3, and 9 mos. recovery breathing clean air. The lungs were carefully removed, inflation fixed with glutaraldehyde and then processed for freeze fracture and transmission electron microscopy of ultra-thin epon sections. Evaluation of tight junctions of bronchioles and alveoli were disrupted in ultrathin sections and freeze fracture replicas during the period of NO2 exposure. Fibril number, length, degree of fragmentation and orientation were different from age matched controls. The bronchiolar tight junctional fibrils were quantitatively reduced in number and fragmented into much smaller fibril lengths. Alveolar tight junctions were qualitatively disrupted in a similar fashion, however, the sites of damage were focal. During recovery tight junctions in bronchioles did not regain normal fibril number, orientation and continuity, based on quantitative assessment, observed in age matched controls. Alveolar tight junctions remained focally altered. This data indicated that chronic NO2 altered morphologic characteristics of epithelial tight junctions of the lung throughout the period of exposure. The repair process during recovery did not restore the normal tight junction ultrastructural organization observed in age controls. This persistent deviation from the normal is likely to alter and compromise airway epithelial barrier function in the lungs of these hamsters.
据报道，急性接触二氧化氮会破坏肺上皮细胞的紧密连接。我们研究了长期接触二氧化氮以及恢复呼吸清洁空气对远端气道和肺泡上皮细胞紧密连接的影响。将叙利亚金黄地鼠暴露于二氧化氮（30 ppm）中5个月或9个月，其中一组暴露9个月的动物被允许恢复呼吸清洁空气3个月或9个月。在接触二氧化氮5个月和9个月后以及恢复呼吸清洁空气3个月和9个月后处死动物。小心取出肺脏，用戊二醛充气固定，然后进行冷冻断裂处理，并对超薄环氧树脂切片进行透射电子显微镜检查。在二氧化氮暴露期间，超薄切片和冷冻断裂复制品中细支气管和肺泡的紧密连接受到破坏。纤维数量、长度、断裂程度和方向与年龄匹配的对照组不同。细支气管紧密连接纤维的数量在定量上减少，并断裂成更短的纤维长度。肺泡紧密连接在质量上以类似方式受到破坏，然而，损伤部位是局部的。在恢复过程中，根据定量评估，细支气管的紧密连接没有恢复到年龄匹配对照组中观察到的正常纤维数量、方向和连续性。肺泡紧密连接仍然局部改变。这些数据表明，长期接触二氧化氮在整个暴露期间改变了肺上皮紧密连接的形态特征。恢复过程中的修复并没有恢复年龄对照组中观察到的正常紧密连接超微结构组织。这种与正常情况的持续偏差可能会改变并损害这些仓鼠肺部气道上皮屏障功能。
