Nitric oxide participates in early events associated with NNMU-induced acute lung injury in rats.
Nitric oxide participates in early events associated with NNMU-induced acute lung injury in rats.
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一氧化氮参与与 NNMU 诱导的大鼠急性肺损伤相关的早期事件。
DOI：
10.1152/ajplung.1999.276.2.l263
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
Moxley,MA
中科院分区：
文献类型：
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作者：
Cruz,WS;Corbett,JA;Longmore,WJ;Moxley,MA
本研究探讨了亚硝基-N-甲基氨基甲酸酯(NNMU)致急性肺损伤的生化机制。NNMU注射后24 h，肺泡灌洗液(BAL)中出现中性粒细胞渗入(占细胞总数的10.58±3.00%；与对照组比较P<0.05)。然而，NNMU诱导的肺泡-动脉血氧分压差升高需要72小时才能形成。给药后24小时开始每日腹腔注射诱导型一氧化氮合酶(⋅)选择性抑制剂氨基胍(AG)，可提高NNMU处理动物的存活率。然而，注射NNMU后48h或72h开始注射AG并不能显著提高NNMU处理动物的存活率。这些结果提示⋅-NO参与了NNMU所致急性肺损伤的早期事件。注射NNMU后24小时和48小时分离的大鼠BAL细胞在体外培养24小时后产生较高水平的⋅、NO和表达iNOS值。在这种体外培养过程中，AG抑制⋅NO的产生，但不影响iNOS的表达，而放线菌素D阻止iNOS的表达，并抑制⋅NO的产生。这些结果表明，NNMU来源的BAL细胞在培养过程中可以刺激iNOS表达和⋅-NO的产生。NNMU染毒48h后，大鼠全肺匀浆中iNOS表达增加，而同一肺来源的BAL细胞则不表达iNOS。提示NNMU致急性肺损伤的发病机制与BAL细胞刺激肺组织诱导型一氧化氮合酶表达和⋅-NO产生有关。
In this study, the biochemical mechanisms by whichN-nitroso-N-methylurethane (NNMU) induces acute lung injury are examined. Polymorphonuclear neutrophil infiltration into the lungs first appears in the bronchoalveolar lavage (BAL) fluid 24 h after NNMU injection (10.58 ± 3.00% of total cells;P< 0.05 vs. control animals). However, NNMU-induced elevation of the alveolar-arterial O2difference requires 72 h to develop. Daily intraperitoneal injections of the inducible nitric oxide (⋅ NO) synthase (iNOS)-selective inhibitor aminoguanidine (AG) initiated 24 h after NNMU administration improve the survival of NNMU-treated animals. However, AG administration initiated 48 or 72 h after NNMU injection does not significantly improve the survival of NNMU-treated animals. These results suggest that ⋅ NO participates in events that occur early in NNMU-induced acute lung injury. BAL cells isolated from rats 24 and 48 h after NNMU injection produce elevated ⋅ NO and express iNOS during a 24-h ex vivo culture. AG attenuates ⋅ NO production but does not affect iNOS expression, whereas actinomycin D prevents iNOS expression and attenuates ⋅ NO production by BAL cells during this ex vivo culture. These results suggest that NNMU-derived BAL cells can stimulate iNOS expression and ⋅ NO production during culture. In 48-h NNMU-exposed rats, iNOS expression is elevated in homogenates of whole lavaged lungs but not in BAL cells derived from the same lung. These findings suggest that the pathogenic mechanism by which NNMU induces acute lung injury involves BAL cell stimulation of iNOS expression and ⋅ NO production in lung tissue.