Third Department of Critical Care Medicine, University of Athens Medical School, Evgenidio Hospital, Athens 115 28, Greece.
Free Radic Biol Med. 2011 Jan 15;50(2):245-53. doi: 10.1016/j.freeradbiomed.2010.10.712. Epub 2010 Nov 7.
We investigated whether hypoxemic resuscitation from hemorrhagic shock prevents lung injury and explored the mechanisms involved. We subjected rabbits to hemorrhagic shock for 60 min by exsanguination to a mean arterial pressure of 40 mm Hg. By modifying the fraction of the inspired oxygen, we performed resuscitation under normoxemia (group NormoxRes, P(a)O(2)=95-105 mm Hg) or hypoxemia (group HypoxRes, P(a)O(2)=35-40 mm Hg). Animals not subjected to shock constituted the sham group (P(a)O(2)=95-105 mm Hg). We performed bronchoalveolar lavage (BAL) fluid, lung wet-to-dry weight ratio, and morphological studies. U937 monocyte-like cells were incubated with BAL fluid from each group. Cell peroxides, malondialdehyde, proteins, and cytokines in the BAL fluid were lower in sham than in shocked animals and in HypoxRes than in NormoxRes animals. The inverse was true for ascorbic acid and reduced glutathione. Lung edema, lung neutrophil infiltration, myeloperoxidase, and interleukin (IL)-8 gene expression were reduced in lungs of HypoxRes compared with NormoxRes animals. A colocalized higher expression of IL-8 and nitrotyrosine was found in lungs of NormoxRes animals compared to HypoxRes animals. The BAL fluid of NormoxRes animals compared with HypoxRes animals exerted a greater stimulation of U937 monocyte-like cells for proinflammatory cytokine release, particularly for IL-8. In the presence of p38-MAPK and Syk inhibitors and monosodium urate crystals, IL-8 release was reduced. We conclude that hypoxemic resuscitation from hemorrhagic shock ameliorates lung injury and reduces oxygen radical generation and lung IL-8 expression.
我们研究了低氧血症复苏是否能预防失血性休克引起的肺损伤，并探讨了其中的机制。我们通过放血使兔子失血性休克 60 分钟，使平均动脉压降至 40mmHg。通过改变吸入氧分数，我们在正常氧合（组 NormoxRes，P(a)O(2)=95-105mmHg）或低氧合（组 HypoxRes，P(a)O(2)=35-40mmHg）下进行复苏。未休克的动物构成假手术组（P(a)O(2)=95-105mmHg）。我们进行支气管肺泡灌洗（BAL）液、肺湿重/干重比和形态学研究。我们将 U937 单核细胞样细胞与每组 BAL 液孵育。与休克动物相比，BAL 液中的细胞过氧化物、丙二醛、蛋白质和细胞因子在假手术动物中较低，而在 HypoxRes 动物中低于 NormoxRes 动物。相反，抗坏血酸和还原型谷胱甘肽则相反。与 NormoxRes 动物相比，HypoxRes 动物的肺水肿、肺中性粒细胞浸润、髓过氧化物酶和白细胞介素（IL）-8 基因表达减少。与 HypoxRes 动物相比，NormoxRes 动物的肺中发现了 IL-8 和硝基酪氨酸的更高表达。与 HypoxRes 动物相比，NormoxRes 动物的 BAL 液对 U937 单核细胞样细胞释放促炎细胞因子的刺激作用更强，特别是对 IL-8。在存在 p38-MAPK 和 Syk 抑制剂和单钠尿酸盐晶体的情况下，IL-8 释放减少。我们得出结论，低氧血症复苏可改善失血性休克引起的肺损伤，并减少氧自由基生成和肺 IL-8 表达。
