Bhalla D K, Rasmussen R E, Tjen S
Department of Community and Environmental Medicine, University of California, Irvine 92717.
Am J Respir Cell Mol Biol. 1990 Aug;3(2):119-29. doi: 10.1165/ajrcmb/3.2.119.
Cytoskeletal perturbations and associated changes in transepithelial transport in rat airways were analyzed after in vivo treatment with cytochalasin D or vinblastine or exposure to ozone (O3). Exposure of O3 or cytochalasin D, but not vinblastine, increased permeability in the bronchoalveolar region. Combined treatment with cytochalasin D and O3 did not increase the effect seen with each agent alone. However, treatment with vinblastine plus 0.8 ppm O3 resulted in a slight enhancement of permeability over that seen with O3 alone. This enhancement was not seen with 2 ppm O3. When cytochalasin and vinblastine treatment were combined, a synergistic effect on bronchoalveolar permeability was seen, suggesting participation of both microfilamentous and microtubular cytoskeletal elements in maintaining the integrity of the bronchoalveolar epithelium. Potentially harmful effects of O3 on cytoskeletal elements were confirmed in rat lung epithelial cells in culture. O3 exposure produced reversible changes in microfilamentous structures comparable to those produced by cytochalasin D. The results of these studies support the hypotheses that the cytoskeleton has a central role in maintenance of respiratory epithelial integrity and that a target for O3 toxicity may be the components of cytoskeleton. These results, however, do not rule out the possibility that treatment with cytoskeleton destabilizing drugs leads to the release of mediators, which in turn contribute to the airway epithelial dysfunction and increased permeability.
在用细胞松弛素D或长春碱进行体内治疗或暴露于臭氧（O₃）后，分析了大鼠气道中的细胞骨架扰动及相关的跨上皮转运变化。暴露于O₃或细胞松弛素D（而非长春碱）会增加支气管肺泡区域的通透性。细胞松弛素D和O₃联合治疗并未增强单独使用每种药物时所观察到的效果。然而，长春碱与0.8 ppm O₃联合治疗导致通透性比单独使用O₃时略有增强。在2 ppm O₃时未观察到这种增强。当细胞松弛素和长春碱联合治疗时，对支气管肺泡通透性产生了协同作用，这表明微丝和微管细胞骨架成分均参与维持支气管肺泡上皮的完整性。在培养的大鼠肺上皮细胞中证实了O₃对细胞骨架成分的潜在有害影响。暴露于O₃会使微丝结构产生与细胞松弛素D所产生的变化相当的可逆性变化。这些研究结果支持以下假设：细胞骨架在维持呼吸道上皮完整性中起核心作用，并且O₃毒性的一个靶点可能是细胞骨架的成分。然而，这些结果并不排除用细胞骨架破坏药物治疗会导致介质释放的可能性，而介质反过来又会导致气道上皮功能障碍和通透性增加。
