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肺组织升至6 h的(3.76±0.89)U/g肺组织;肺组织病理损伤严重。但抗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。
Objective To study the pathogenic role of extracellular histones in the pathogenesis of acute lung injury (ALl) 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 ana- lyzed 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 his- tone H4 level went up sharply from normal (0.43±0. 11) μg/ml to ( 10. 41±4. 63) μg/ml at 6 h after injection; at the same time the arterial oxygen (PaO2 ) decreased dramatically from normal (97.85±7. 88) mm Hg to (48.83±18.46) mm Hg, 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.