Protective Effect of Carbon Monoxide Inhalation on Lung Injury After Hemorrhagic Shock/Resuscitation in Rats
Protective Effect of Carbon Monoxide Inhalation on Lung Injury After Hemorrhagic Shock/Resuscitation in Rats
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DOI：
10.1097/ta.0b013e3181bbd516
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发表时间：
2010-07-01
影响因子：
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通讯作者：
Morita, Kiyoshi
中科院分区：
文献类型：
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作者：
Kanagawa, Fumitoshi;Takahashi, Toru;Morita, Kiyoshi
背景：失血性休克复苏(HSR)可引起肺部炎症，导致急性肺损伤。一氧化碳(CO)是血红素催化的副产物，被证明具有强大的细胞保护和抗炎作用。本研究旨在探讨低浓度一氧化碳吸入对高铁致大鼠肺损伤的影响。方法：采用失血性高铁致大鼠平均动脉压30 mm Hg，持续60min，然后根据需要进行失血复苏和生理盐水复苏。结果：HSR可引起肺组织核因子-kappaB和激活蛋白-1的DNA结合活性增加，进而上调肺组织中肿瘤坏死因子-α、诱导型一氧化氮合酶和白介素10的基因表达。高铁还导致肺组织髓过氧化物酶活性和湿/干重比值增加，肺组织病理改变更为明显，包括充血、水肿、细胞浸润和出血。相比之下，吸入一氧化碳显著改善了这些炎症事件，组织学变化较少，炎症介质上调较少，核因子-kappaB和激活蛋白-1的激活较少。有趣的是，CO对肺损伤的保护作用与肺组织IL-10mRNA表达的进一步增加有关。结论：低浓度CO可减轻HSR诱导的肺损伤，并通过上调抗炎IL-10水平减轻炎症级联反应。
Background: Hemorrhagic shock and resuscitation (HSR) induces pulmonary inflammation that leads to acute lung injury. Carbon monoxide (CO), a by-product of heme catalysis, was shown to have potent cytoprotective and anti-inflammatory effects. The aim of this study was to examine the effects of CO inhalation at low concentration on lung injury induced by HSR in rats.Methods: Rats were subjected to HSR by bleeding to achieve mean arterial pressure of 30 mm Hg for 60 minutes followed by resuscitation with shed blood and saline as needed to restore blood pressure. HSR animals were either maintained in room air or were exposed to CO at 250 ppm for 1 hour before and 3 hours after HSR.Results: HSR caused an increase in the DNA binding activity of nuclear factor-kappa B and activator protein-1 in the lung followed by the up-regulation of pulmonary gene expression of tumor necrosis factor-alpha, inducible nitric oxide synthase, and interleukin (IL)-10. HSR also resulted in an increase in myeloperoxidase activity and wet weight to dry weight ratio in the lung, and more prominent histopathologic changes including congestion, edema, cellular infiltration, and hemorrhage. In contrast, CO inhalation significantly ameliorated these inflammatory events as judged by fewer histologic changes, less up-regulation of inflammatory mediators, and less activation of nuclear factor-kappa B and activator protein-1. Interestingly, the protective effects against lung injury afforded by CO were associated with further increases in mRNA expression of IL-10 in the lung.Conclusions: These findings suggest that inhaled CO at a low concentration ameliorated HSR-induced lung injury and attenuated inflammatory cascades by up-regulation of anti-inflammatory IL-10.