Postinsult treatment with N-acetyl-L-cysteine decreases IL-1-induced neutrophil influx and lung leak in rats.
Postinsult treatment with N-acetyl-L-cysteine decreases IL-1-induced neutrophil influx and lung leak in rats.
复制标题
N-乙酰基-L-半胱氨酸的攻击后处理可减少大鼠中 IL-1 诱导的中性粒细胞流入和肺渗漏。
DOI：
10.1152/ajplung.1993.265.5.l501
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发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Repine,JE
中科院分区：
文献类型：
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作者：
Leff,JA;Wilke,CP;Hybertson,BM;Shanley,PF;Beehler,CJ;Repine,JE
我们发现，气管内注射白细胞介素1α(IL-1)迅速(5h)增加了125I标记的白蛋白从血液渗入肺内(肺渗漏)、中性粒细胞流入肺灌洗液、肺组织氧化谷胱甘肽(GSSG)水平、呼吸过氧化氢(H_2O_2)浓度以及肺组织学异常。由于N-乙酰-L-半胱氨酸在体内升高谷胱甘肽水平，在体外清除氧自由基，我们观察了静脉注射N-乙酰-L半胱氨酸对气管内注射IL-1后肺组织变化的影响。我们发现，在气管内注射IL-1之前或之后立即给予NAC可减少肺渗漏、中性粒细胞流入肺灌洗液，并减少肺组织学缺陷。NAC治疗还能增加气管内注射IL-1大鼠的血中酸溶巯基水平，减少肺GSSG升高，降低呼吸中的过氧化氢水平。后者的发现与NAC增强谷胱甘肽或其他巯基的可能性一致，结果是减少了由于过氧化氢或过氧化氢衍生产物造成的氧化应激。由于NAC在这种相关的完整的急性肺损伤动物模型中是有效的，我们推测NAC在成人呼吸窘迫综合征患者的治疗中可能有希望。
We found that intratracheal administration of interleukin-1 alpha (IL-1) rapidly (5 h) increased leak of 125I-labeled albumin from the blood into the lung (lung leak), influx of neutrophils into lung lavages, lung oxidized glutathione (GSSG) levels, breath hydrogen peroxide (H2O2) concentrations, and lung histological abnormalities in intact rats. Since N-acetyl-L-cysteine (NAC) increases glutathione (GSH) levels in vivo and scavenges oxygen radicals in vitro, we tested the effect of NAC given intravenously on lung changes following intratracheal IL-1 administration. We found that administration of NAC immediately before or 2.5 h after intratracheal administration of IL-1 decreased lung leak, neutrophil influx into lung lavages, and defects in lung histology. NAC treatment also increased blood acid soluble sulfhydryl levels, reduced lung GSSG increases, and decreased breath H2O2 levels in rats given IL-1 intratracheally. The latter findings are consistent with the possibility that NAC is enhancing GSH or other sulfhydryls and, as a result, reducing oxidative stress due to H2O2 or H2O2-derived products. Since postinsult treatment with NAC is effective in this relevant intact animal model of acute lung injury, we speculate that NAC may have promise in the treatment of patients with the adult respiratory distress syndrome.