The Role of Nitric Oxide in Hyperoxia Induced Lung Injury

一氧化氮於高濃度氧氣誘發肺損傷之角色

康柏皇(Bor-Hwang Kang) ； 萬芳榮(Fang-Jung Wan) ； 吳其中(Chi-Chung Wu)

《Journal of Medical Sciences》 21卷1期 (2001/02) Pp. 20-31

摘要

本研究探討一氧化氮於高濃度氧氣誘發肺損傷與動物死亡中所扮演之角色。將大白鼠暴露於100%氧氣或空氣中達60小時，每隔12小時，取血液樣本以測量一氧化氮代謝物含量。另一組動物，於氧氣暴露開始前及開始後24小時，經腹腔注射給予一氧化氮合成酶抑制劑L-NAME，觀察動物於100%氧氣中之存活時間。第三組動物於氧氣暴露開始前，給予L-NAME，於氧氣暴露24小時後，進行心室取血、肺灌洗、取肺組織，以分析一氧化氮代謝物含量、肺損傷及中性白血球之入侵情形。我們發現，氧氣暴露可引發全身一氧化氮含量增加。抑制一氧化氮合成酶則使得動物於氧氣中之存活時間縮短。同時，一氧化氮合成酶抑制劑可增加肺中白血球之入侵。這些結果顯示，一氧化氮在氧氣毒性中扮演保護性之角色，而抑制一氧化氮合成酶的傷害性效果可能與增加肺中白血球之入侵有關。

關鍵字

高濃度氧氣 ； 一氧化氮 ； 肺損傷 ； 中性白血球

並列摘要

The present study was designed to evaluate the role of nitric oxide, a free radical and physiological messenger, in hyperoxia-induced lung injury and animal death. SD rats were exposed to 100% oxygen or room air for 60 hours. Blood samples were obtained every 12 hours for the measurement of NO metabolites. In the second set of animals, rats were injected intraperitoneally with a nitric oxide synthase inhibitor, L-NAME (25 or 50 mg/kg) immediately before and 24 hours after the beginning of 100% oxygen exposure. Control animals received normal saline injection. They were exposed to hyperoxia until death. The survival rate of different animal groups were recorded and compared. In the third set, rats received a single injection of L-NAME (25 mg/kg) or saline before 100% oxygen exposure. Twenty-four hours after hyperoxic exposure, animals were sacrificed and underwent broncho-alveolar lavage (BAL). The BAL fluid was used for the analyses of cell counts, LDH level, protein concentration, and NO content. Before BAL, blood samples were obtained from right ventricle for NO content determination. The lavaged lungs were collected for the measurement of myeloperoxidase (MPO) level, an indicator of neutrophil content. The results showed that plasma NO content was significantly increased after 48 and 60 hours of hyperoxic exposure. Further, L-NAME treatment shortened the survival time of hyperoxia-exposed rats in a dose-dependent manner. In the 24 h exposure groups, we observed that 24 hours of hyperoxia increased plasma NO content, and protein concentration in BAL fluid. Pretreatment with a single dose of L-NAME (25 mg/kg) did not significantly alter parameters of BAL fluid. However, L-NAME significantly increased MPO content in the lung tissue. Taken together, these results suggest that nitric oxide may have a protective role during normobaric hyperoxic exposure. The detrimental effect of L-NAME may be partly related to increased inflammatory cell infiltration.

並列關鍵字

hyperoxia ； nitric oxide ； lung injury ； neutrophils