van Klaveren R J, Roelant C, Boogaerts M, Pype J L, Demedts M, Nemery B
Laboratory of Pneumology, Unit of Lung Toxicology, K.U. Leuven, Herestraat 49, B-3000 Leuven, Belgium.
Pulm Pharmacol Ther. 1998 Feb;11(1):23-30. doi: 10.1006/pupt.1998.0114.
The aims of this study were to investigate the effect of hyperoxia on O2(-.), H2O2 and .NO generation and iNOS mRNA levels in rat type II pneumocytes in vitro and the possible protective effect of the lazaroid U-74389G. Rat type II pneumocytes were exposed, 36 h after isolation, to air, 60% or 85% O2 for 48 h. At the beginning of the experiment and 24 h later, the cells were exposed for 30 min to either 30 microM U-74389G or only the vehicle for the lazaroid (control). Exposure to 60% and 85% O2 decreased nitrite production 2.9-fold and 3.9-fold, and increased O2(-.) and H2O2 generation 4.6-fold and 6.7-fold, respectively. In the 85% O2-exposed cells, hyperoxia increased lipid peroxidation (thiobarbituric acid reactive substances, TBARS production) 2-fold and iNOS mRNA production 5.4-fold. U-74389G prevented the decrease in nitrite and the rise in O2(-.) and H2O2 production, the increase in TBARS and the rise in iNOS mRNA after hyperoxia. We conclude that exposure of type II pneumocytes in vitro to subtoxic oxygen levels leads to a disturbance in the .NO-O2(-.) balance despite increased iNOS mRNA levels. The lazaroid U-74389G appears to be a useful compound in the protection of hyperoxic lung injury by restoration of this .NO-O2(-.) balance and prevention of TBARS formation.
本研究旨在探讨高氧对体外培养的大鼠Ⅱ型肺泡上皮细胞中O2(-.)、H2O2和.NO生成以及诱导型一氧化氮合酶（iNOS）mRNA水平的影响，以及拉扎罗类药物U-74389G可能的保护作用。大鼠Ⅱ型肺泡上皮细胞在分离36小时后，分别暴露于空气、60%或85%氧气环境中48小时。在实验开始时和24小时后，细胞分别暴露于30μM U-74389G或仅暴露于拉扎罗类药物的溶剂（对照组）30分钟。暴露于60%和85%氧气环境分别使亚硝酸盐生成减少2.9倍和�3.9倍，而O2(-.)和H2O2生成分别增加4.6倍和6.7倍。在暴露于85%氧气的细胞中，高氧使脂质过氧化（硫代巴比妥酸反应性物质，TBARS生成）增加2倍，iNOS mRNA生成增加5.4倍。U-74389G可防止高氧后亚硝酸盐生成的减少、O2(-.)和H2O2生成的增加、TBARS的增加以及iNOS mRNA的升高。我们得出结论，体外培养的Ⅱ型肺泡上皮细胞暴露于亚毒性氧水平会导致.NO - O2(-.)平衡紊乱，尽管iNOS mRNA水平升高。拉扎罗类药物U-74389G似乎是一种有用的化合物，可通过恢复这种.NO - O2(-.)平衡和防止TBARS形成来保护高氧肺损伤。
