Schwartz M D, Repine J E, Abraham E
Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver 80262, USA.
Am J Respir Cell Mol Biol. 1995 Apr;12(4):434-40. doi: 10.1165/ajrcmb.12.4.7695923.
Acute inflammatory lung injury often complicates hemorrhagic shock, a systemic ischemia-reperfusion syndrome. Because oxygen radicals are generated during ischemia-reperfusion, and oxygen radicals can activate nuclear regulatory factors that affect transcription of proinflammatory cytokines, we examined the premise that oxygen radicals increase interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) expression in lung mononuclear cells after hemorrhage. Intraparenchymal pulmonary mononuclear cells isolated 1 h after hemorrhage from control mice had increased levels of mRNA for IL-1 beta (P < 0.001) and TNF-alpha (P < 0.05) compared with cells from sham-hemorrhaged mice. Hemorrhaged mice treated with the oxygen radical scavenger dimethylthiourea (DMTU) had decreased levels of mRNA for IL-1 beta in pulmonary mononuclear cells, compared with hemorrhaged controls (P < 0.05). In hemorrhaged mice depleted of xanthine oxidase (XO) by a tungsten-enriched diet, pulmonary mononuclear cell mRNA levels for IL-1 beta and TNF-alpha were significantly decreased (P < 0.01 and 0.05, respectively), compared with cells from hemorrhaged control mice fed a normal diet. Similarly, mRNA transcripts for IL-1 beta and TNF-alpha among pulmonary mononuclear cells from hemorrhaged mice treated with allopurinol, an inhibitor of XO, were also significantly reduced (P < 0.05 and 0.001, respectively), compared with hemorrhaged control mice not treated with allopurinol. Our results indicate that XO-derived oxygen radicals contribute to the increased expression of mRNA for IL-1 beta and TNF-alpha, which occurs among pulmonary mononuclear cell populations immediately after hemorrhage.(ABSTRACT TRUNCATED AT 250 WORDS)
急性炎症性肺损伤常使出血性休克（一种全身性缺血再灌注综合征）复杂化。由于缺血再灌注过程中会产生氧自由基，且氧自由基可激活影响促炎细胞因子转录的核调节因子，我们检验了这样一个假设：出血后氧自由基会增加肺单核细胞中白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）的表达。与假出血小鼠的细胞相比，从对照小鼠出血1小时后分离出的肺实质内肺单核细胞中，IL-1β（P < 0.001）和TNF-α（P < 0.05）的mRNA水平升高。与出血对照组相比，用氧自由基清除剂二甲基硫脲（DMTU）处理的出血小鼠肺单核细胞中IL-1β的mRNA水平降低（P < 0.05）。在通过富含钨的饮食耗尽黄嘌呤氧化酶（XO）的出血小鼠中，与喂食正常饮食的出血对照小鼠的细胞相比，肺单核细胞中IL-1β和TNF-α的mRNA水平显著降低（分别为P < 0.01和0.05）。同样，与未用别嘌呤醇处理的出血对照小鼠相比，用XO抑制剂别嘌呤醇处理的出血小鼠肺单核细胞中IL-1β和TNF-α的mRNA转录物也显著减少（分别为P < 0.05和0.001）。我们的结果表明，XO衍生的氧自由基促成了出血后立即在肺单核细胞群体中出现的IL-1β和TNF-α mRNA表达增加。（摘要截断于250字）
