细胞外组蛋白在酸吸入性急性肺损伤发病中的作用研究

Study in the role of extracellular histones in the pathogenesis of acute lung injury caused by acid aspiration

目的 研究细胞外组蛋白是否是盐酸吸入性急性肺损伤（ALI）发病过程中的重要炎症介质,是否可作为干预的靶标.方法 选取生理盐水和4个浓度的盐酸（0.01、0.1、0.3和0.5mol/L）来研究小鼠吸入盐酸与血浆组蛋白水平的相关性;选取吸入盐酸后共6个时间点（1、3、6、12、24和72 h）观察组蛋白的变化规律;采用抗组蛋白中和抗体研究特异拮抗组蛋白对小鼠病死率、血气分析、肺水肿、肺组织MPO活力、肺病理的影响.结果 小鼠吸入盐酸后血浆中组蛋白水平明显升高,而且吸入盐酸浓度与血浆中组蛋白H4水平具有明显的正相关性（r=0.874 6,P=0.031 7）.抗组蛋白H4中和抗体可减少病死率（P=0.034 5）,血气分析结果有所改善,肺水肿、肺组织髓过氧化物酶（MPO）活力、肺组织病理均有改变.结论 细胞外组蛋白是一种新的内源性炎性介质,在介导酸吸入性ALI中起重要作用;它既可作为反映损伤严重程度的指标,还可作为干预治疗的靶标.

Objective To investigate the effects of extracellular histones as a major mediator and the target for intervention in the pathogenesis of ALI in the wake of acid aspiration.Methods The correlation of circulating histones and aspiratory acid was determined with normal saline and 4 different concentrations of acid （0.01 mol/L,0.1 mol/L,0.3 mol/L and 0.5 mol/L）.The dynamic change of circulating histones was observed at 6 intervals of 1,3,6,12,24 and 72 h after injury.The protection of anti-histone-4 antibody was assessed by survival rates,blood gas,lung edema,MPO activity and lung pathological change.Results After acid aspiration,extracellular histone H4 increased significantly.The circulating histone levels were closely correlative with the concentrations of aspiratory acid （r =0.874 6,P =0.031 7）.The anti-histone-4 antibody could decrease mortality （P =0.034 5） and improve blood gas,lung edema,MPO activity and lung pathological change.Conclusions The results showed that extracellular histornes were not only the key mediators in the pathogenesis of ALI but also the target for intervention.