Changes in structure, mechanics, and insulin-like growth factor-related gene expression in the lungs of newborn rats exposed to air or 60% oxygen
Changes in structure, mechanics, and insulin-like growth factor-related gene expression in the lungs of newborn rats exposed to air or 60% oxygen
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DOI：
10.1203/00006450-199606000-00001
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发表时间：
1996-06-01
影响因子：
3.6
通讯作者：
Tanswell, AK
中科院分区：
文献类型：
--
作者：
Han, RNN;Buch, S;Tanswell, AK
暴露于大于或等于95%O-2的新生大鼠2周，一个广泛使用的模型的氧化剂/抗氧化剂的相互作用，在新生儿肺损伤，结果在逮捕肺生长不发育不良的病变中观察到的慢性人类新生儿肺损伤。为了确定是否发育不良的肺细胞生长将被视为在较低的O-2浓度，我们暴露新生大鼠要么95%O-2 1周，然后60%O-2 1周，或60%O-2 2周。暴露于95%O-2 1wk显著抑制肺DNA合成。在60%O-2中的第2周期间，合成没有恢复，肺组织中也没有明显的发育不良生长区域。相比之下，连续2周暴露于60%O-2导致肺重量略有增加，肺体积在一定范围内的充气压力显着减少。还观察到肺细胞DNA合成的总体但不均匀的减少。受影响的细胞类型的初步分析表明，抑制DNA合成影响内皮细胞比间质细胞，而DNA合成增加II型肺细胞。DNA合成减少的区域散布着片状的实质增厚和DNA合成活跃的区域。这些实质增厚的区域，而不是其他区域，免疫反应性IGF-I和I型IGF受体增加。这些数据与O-2对生长因子和生长因子受体表达的直接影响一致，导致慢性新生儿肺损伤中肺细胞发育不良。
Exposure of neonatal rats to greater than or equal to 95% O-2 for 2 wk, a widely used model of oxidant/antioxidant interactions in neonatal lung injury, results in arrested lung growth without the dysplastic lesions observed in chronic human neonatal lung injury. To determine whether dysplastic lung cell growth would be seen at lesser O-2 concentrations, we exposed newborn rats to either 95% O-2 for 1 wk followed by 60% O-2 for 1 wk, or to 60% O-2 for 2 wk. Exposure to 95% O-2 for 1 wk profoundly inhibited lung DNA synthesis. Recovery of synthesis did not occur during the 2nd wk in 60% O-2, nor were areas of dysplastic growth evident in lung tissue. In contrast, a continuous 2-wk exposure to 60% O-2 resulted in a slight increase in lung weight with a significant reduction in lung volume over a range of inflation pressures. Also seen was an overall, but inhomogeneous, reduction in lung cell DNA synthesis. A preliminary analysis of affected cell types suggested that inhibition of DNA synthesis affected endothelial cells more than interstitial cells, whereas DNA synthesis increased in type II pneumocytes. Areas of reduced DNA synthesis were interspersed with patchy areas of parenchymal thickening and active DNA synthesis. These areas of parenchymal thickening, but not other areas, had increased immunoreactive IGF-I and the type I IGF receptor. These data are consistent with a direct effect of O-2 on growth factor and growth factor receptor expression in causing dysplastic lung cell growth in chronic neonatal lung injury.