Oxidant stress mediates inflammation and apoptosis in ventilator-induced lung injury.
Oxidant stress mediates inflammation and apoptosis in ventilator-induced lung injury.
复制标题
氧化应激介导呼吸机引起的肺损伤中的炎症和细胞凋亡。
DOI：
10.1111/j.1440-1843.2008.01279.x
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Quinn,DeborahA
中科院分区：
文献类型：
--
作者：
Syrkina,Olga;Jafari,Behrouz;Hales,CharlesA;Quinn,DeborahA
背景与目的：呼吸机诱导的肺损伤(VILI)可导致呼吸道上皮细胞凋亡和肺部炎症。在活体大潮气量的呼吸机能诱导MIP-2的产生、肺中性粒细胞的隔离和呼吸道细胞的凋亡。目的：探讨氧自由基清除剂N-乙酰半胱氨酸对大鼠肺组织炎症和细胞凋亡的影响。方法：SD大鼠(n= ，n=5)在低潮气量(VT7 m L/kg)和大潮气量(VT 2 0 m L/kg)下分别给予或不给予NAC 14 0 mg/kg。结果：通气量为20 /kg时，肺泡灌洗液中中性粒细胞浸润、肺泡灌洗液中MIP-2、肿瘤坏死因子- 和白介素6含量及肺上皮细胞凋亡率均明显高于对照组，肺组织中主要抗氧化剂谷胱甘肽含量明显降低。与未加NAC的VT20 m L/kg通气组比较，VT20 m L/kg通气组大鼠肺组织谷胱甘肽水平降低，血清异前列腺素水平、中性粒细胞浸润、肺泡灌洗液中细胞因子和细胞凋亡显著降低(P<； 0.0 5)。结论：氧化诱导炎症和细胞凋亡在VILI发病中起早期作用。
Background and objective:Ventilator‐induced lung injury (VILI) leads to airway epithelial cell apoptosis and lung inflammation. High tidal volume ventilationin vivohas been shown to induce MIP‐2 production, lung neutrophil sequestration and apoptotic airway cell death. This study aimed to determine the effect of N‐acetylcysteine (NAC), a scavenger of oxygen radicals, on lung inflammation and apoptosis in anin vivomodel of VILI.Methods:Sprague–Dawley rats (n= 5 per group) were ventilated at low tidal volume (VT7 mL/kg) or high tidal volume (VT20 mL/kg) with or without administration of 140 mg/kg of intravenous NAC. Animals were ventilated for 30 min, 1 or 2 h, then allowed to recover for 2 h, at which time neutrophil infiltration, MIP‐2, TNF‐α and IL‐6 in BAL fluid, as well as the percentage of apoptotic airway epithelial cells, were measured.Results:Ventilation at VT20 mL/kg increased oxidant release, as measured by serum isoprostane, and decreased lung glutathione, the major antioxidant in the lung. NAC treatment during ventilation at VT20 mL/kg prevented the decrease in lung glutathione and significantly lowered serum isoprostane levels, neutrophil infiltration, cytokines in the BAL and apoptosis in the airways as compared with animals ventilated at VT20 mL/kg without NAC (P< 0.05).Conclusions:These data point to an early role of oxidant‐induced inflammation and apoptosis in VILI.