细胞外组蛋白在油酸所致急性肺损伤中的作用

Role of extracellular histones in oleic acid-induced acute lung injury in rats

关键词: 急性肺损伤  油酸  细胞外组蛋白  炎症

Keywords: acute lung injury  oleic acid  extracellular histones  inflammation

摘 要: 目的 研究细胞外组蛋白在大鼠急性肺损伤（ALI）发病过程中的作用。方法 大鼠静脉注射油酸（OA）0.15 ml/kg复制ALI模型，在不同时间点检测血浆中细胞外组蛋白、动脉血气、肺组织MPO活性、肺组织病理改变；同时验证抗组蛋白H4抗体对肺损伤的保护作用。结果 注射OA后，大鼠血浆中组蛋白明显增加，组蛋白H4浓度从正常时的（0.43±0.11）μg/ml升高至6 h的（10.41±4.63）μg/ml；动脉血氧分压明显降低，从正常时的（97.85±7.88）mm Hg降至6 h的（48.83±18.46）mm Hg；肺水肿的标志肺湿/干质量比值由正常时的3.38±0.46升高至6 h的8.17±2.31；肺组织MPO活性增高，由正常的（1.35±0.18）U/g肺组织降至6 h的（3.76±0.89）U/g肺组织；肺组织病理损伤严重。但是，抗H4抗体预处理可明显拮抗肺损伤。结论 细胞外组蛋白在ALI的炎症性损伤反应中起重要的保护作用。

Abstract: Objective To study the pathogenic role of extracellular histones in the pathogenesis of acute lung injury (ALI) in rats. Methods: The animal model of ALI was produced by intravenous injection of oleic acid (0.15 ml/kg body mass) in rats. The plasmic level of extracellular histones , blood gas, , MPO activity in lung tissues and lung pathological change were analyzed at different time points after injection. Additionally, the protective effect of anti-H4 antibody was assessed as well. Results: The levels of extracellular histones in plasma were increased obviously after intravenous injection of oleic acid in rats, the histone H4 level went up sharply from normal 0.43±0.11μg/ml to 10.41±4.63μg/ml at 6h after injection; at the same time the arterial oxygen pressure (PaO2) decreased dramatically from normal 97.85±7.88 mmHg to 48.83±18.46mmHg, the lung wet/dry weight ratio, a hallmark of lung edema, increased obviously from normal 3.38±0.46 to 8.17±2.31, while the lung MPO activity increased sharply from normal 1.35±0.18 U/g lung tissue to 3.76±0.89 U/g , and the pathological change in lung tissue was very serious. On the other hand, pre-treatment with anti-H4 antibody showed good antagonism effect to lung injury. Conclusion: Extracellular histones could play a contributory role towards inflammatory damage in ALI.