Aoki Takuya, Yamasawa Fumihiro, Kawashiro Takeo, Shibata Tetsuichi, Ishizaka Akitoshi, Urano Tetsuya, Okada Yasumasa
Respiratory Division, Department of Internal Medicine, School of Medicine, Tokai University, Isehara, Japan.
Respir Res. 2008 Apr 26;9(1):37. doi: 10.1186/1465-9921-9-37.
The patient population receiving long-term oxygen therapy has increased with the rising morbidity of COPD. Although high-dose oxygen induces pulmonary edema and interstitial fibrosis, potential lung injury caused by long-term exposure to low-dose oxygen has not been fully analyzed. This study was designed to clarify the effects of long-term low-dose oxygen inhalation on pulmonary epithelial function, edema formation, collagen metabolism, and alveolar fibrosis.
Guinea pigs (n = 159) were exposed to either 21% or 40% oxygen for a maximum of 16 weeks, and to 90% oxygen for a maximum of 120 hours. Clearance of inhaled technetium-labeled diethylene triamine pentaacetate (Tc-DTPA) and bronchoalveolar lavage fluid-to-serum ratio (BAL/Serum) of albumin (ALB) were used as markers of epithelial permeability. Lung wet-to-dry weight ratio (W/D) was measured to evaluate pulmonary edema, and types I and III collagenolytic activities and hydroxyproline content in the lung were analyzed as indices of collagen metabolism. Pulmonary fibrotic state was evaluated by histological quantification of fibrous tissue area stained with aniline blue.
The clearance of Tc-DTPA was higher with 2 week exposure to 40% oxygen, while BAL/Serum Alb and W/D did not differ between the 40% and 21% groups. In the 40% oxygen group, type I collagenolytic activities at 2 and 4 weeks and type III collagenolytic activity at 2 weeks were increased. Hydroxyproline and fibrous tissue area were also increased at 2 weeks. No discernible injury was histologically observed in the 40% group, while progressive alveolar damage was observed in the 90% group.
These results indicate that epithelial function is damaged, collagen metabolism is affected, and both breakdown of collagen fibrils and fibrogenesis are transiently induced even with low-dose 40% oxygen exposure. However, these changes are successfully compensated even with continuous exposure to low-dose oxygen. We conclude that long-term low-dose oxygen exposure does not significantly induce permanent lung injury in guinea pigs.
随着慢性阻塞性肺疾病（COPD）发病率的上升，接受长期氧疗的患者数量有所增加。尽管高剂量氧气会诱发肺水肿和间质纤维化，但长期暴露于低剂量氧气所导致的潜在肺损伤尚未得到充分分析。本研究旨在阐明长期低剂量吸氧对肺上皮功能、水肿形成、胶原代谢和肺泡纤维化的影响。
将159只豚鼠分别暴露于21%或40%的氧气中最长16周，以及暴露于90%的氧气中最长120小时。吸入的锝标记二乙三胺五乙酸（Tc-DTPA）的清除率和支气管肺泡灌洗液与血清白蛋白（ALB）的比值（BAL/血清）用作上皮通透性的标志物。测量肺湿重与干重之比（W/D）以评估肺水肿，并分析肺中I型和III型胶原酶活性及羟脯氨酸含量作为胶原代谢指标。通过对苯胺蓝染色的纤维组织面积进行组织学定量来评估肺纤维化状态。
暴露于40%氧气2周时，Tc-DTPA的清除率更高，而40%组和21%组之间的BAL/血清白蛋白和W/D没有差异。在40%氧气组中，2周和4周时的I型胶原酶活性以及2周时的III型胶原酶活性增加。2周时羟脯氨酸和纤维组织面积也增加。在40%组中组织学上未观察到明显损伤，而在90%组中观察到进行性肺泡损伤。
这些结果表明，即使暴露于低剂量40%氧气，上皮功能也会受损，胶原代谢会受到影响，并且胶原纤维的分解和纤维生成都会被短暂诱导。然而，即使持续暴露于低剂量氧气，这些变化也能成功得到代偿。我们得出结论，长期低剂量氧气暴露不会在豚鼠中显著诱发永久性肺损伤。
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