Antiinflammatory properties of inducible nitric oxide synthase in acute hyperoxic lung injury
Antiinflammatory properties of inducible nitric oxide synthase in acute hyperoxic lung injury
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DOI：
10.1165/ajrcmb.24.4.4218
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发表时间：
2001-04-01
影响因子：
6.4
通讯作者：
Jones, RC
中科院分区：
文献类型：
--
作者：
Kobayashi, H;Hataishi, R;Jones, RC
本研究的目的是确定是否内源性一氧化氮（NO），特别是诱导型NO合酶亚型（iNOS：NOS II），减少或放大小鼠在高氧分压呼吸肺损伤。以前的研究表明，外源性（吸入）NO保护对高氧诱导的肺损伤，和内源性NO来源于iNOS抑制白细胞募集和保护对脂多糖诱导的肺损伤。在本研究中，通过支气管肺泡灌洗液（BALF）中白蛋白和乳酸脱氢酶水平升高以及血管外肺水增加，高氧（> 98%O-2，持续72 h）诱导野生型和iNOS缺陷型小鼠急性肺损伤。iNOS缺陷小鼠的肺损伤比野生型小鼠更严重，并且与BALF中多形核白细胞数量增加相关。野生型高氧小鼠肺中iNOS信使RNA表达水平增加。硝基酪氨酸，反应性NO物种的标志物，在野生型和iNOS缺陷型小鼠在高氧中表达，表明蛋白质硝化的iNOS非依赖性途径。我们得出结论，iNOS能够减少肺白细胞积聚和肺损伤。这些数据表明，诱导型一氧化氮合酶诱导作为一种保护机制，以尽量减少急性暴露于高氧的影响。
The objective of this study was to determine whether endogenous nitric oxide (NO), specifically the inducible NO synthase isoform (iNOS: NOS II), reduces or amplifies lung injury in mice breathing at a high oxygen tension. Previous studies have shown that exogenous (inhaled) NO protects against hyperoxia-induced lung injury, and that endogenous NO derived from iNOS inhibits leukocyte recruitment and protects against lung injury induced by lipopolysaccharide. In the present study, hyperoxia (> 98% O-2 for 72 h) induced acute lung injury in both wild-type and iNOS-deficient mice as determined by elevated albumin and lactate dehydrogenase levels in bronchoalveolar lavage fluid (BALF) and by increased extravascular lung water. Lung injury was greater in iNOS-deficient mice than in wild-type mice and was associated with an increased number of polymorphonuclear leukocytes in BALF. iNOS messenger RNA expression levels increased in the lungs of wild-type hyperoxic mice. Nitrotyrosine, a marker of reactive NO species, was expressed in both wild-type and iNOS-deficient mice in hyperoxia, indicating an iNOS-independent pathway for protein nitration, We conclude that iNOS is capable of reducing pulmonary leukocyte accumulation and lung injury. The data indicate that iNOS induction serves as a protective mechanism to minimize the effects of acute exposure to hyperoxia.