Thet L A, Parra S C, Shelburne J D
Am Rev Respir Dis. 1984 Jan;129(1):174-81. doi: 10.1164/arrd.1984.129.1.174.
We studied the repair of lung injury in adult rats exposed to 100% oxygen for 60 h, then placed in ambient air. Lung ornithine decarboxylase (ODC) activity and polyamine (putrescine, spermidine, and spermine) content during repair were correlated with changes in lung ultrastructure. The effect of difluoromethylornithine (DFMO), a selective Irreversible ODC inhibitor, was also studied; ODC activity increased to 25-fold baseline 2 days after injury and returned to normal by 7 days. Polyamine content increased to 3-fold baseline during the first 3 days. During the same period, the number of capillary endothelial cells and the capillary surface area almost doubled, and the number of type 2 epithelial cells increased 2.5-fold. The DFMO treatment lowered ODC activities below baseline, reduced the increase in polyamine content, and also reduced the morphometric parameters described above to only 60 to 70% of the values during normal repair. It also caused a significant decrease in the number of type 1 epithelial cells during repair, suggesting that deficient replacement by differentiating type 2 epithelial cells occurred. We conclude that marked changes in lung ODC activity and polyamine content occur during the repair of oxygen-induced injury to the lung and that selective inhibition of these changes adversely affects repair.
我们研究了成年大鼠暴露于100%氧气60小时后再置于环境空气中时肺损伤的修复情况。修复过程中肺鸟氨酸脱羧酶（ODC）活性和多胺（腐胺、亚精胺和精胺）含量与肺超微结构的变化相关。还研究了选择性不可逆ODC抑制剂二氟甲基鸟氨酸（DFMO）的作用；损伤后2天ODC活性增加至基线的25倍，7天恢复正常。多胺含量在最初3天增加至基线的3倍。在此期间，毛细血管内皮细胞数量和毛细血管表面积几乎增加了一倍，Ⅱ型上皮细胞数量增加了2.5倍。DFMO处理使ODC活性降至基线以下，减少了多胺含量的增加，还将上述形态学参数降低至正常修复期间值的仅60%至70%。它还导致修复过程中Ⅰ型上皮细胞数量显著减少，表明发生了Ⅱ型上皮细胞分化替代不足的情况。我们得出结论，在氧诱导的肺损伤修复过程中，肺ODC活性和多胺含量发生显著变化，选择性抑制这些变化会对修复产生不利影响。
