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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 role of extracellular histones in the pathogenesis of acute lung injury (ALI) in rats. Methods The rat model of ALI was induced by intraperitoneal injection of 0.15 ml / kg oleic acid (OA). The plasma levels of extracellular histone protein, arterial blood gas, MPO activity and lung pathological changes were measured at different time points. Simultaneously, anti-histone H4 antibody Protection of lung injury. Results After the injection of OA, the level of histone H4 in rat plasma increased significantly from (0.43 ± 0.11) μg / ml to (10.41 ± 4.63) μg / ml at 6 h; the arterial partial pressure of oxygen Decreased significantly from (97.85 ± 7.88) mmHg to (48.83 ± 18.46) mmHg at 6 h; the lung wet / dry mass ratio of pulmonary edema markedly increased from 3.38 ± 0.46 at normal to 6 h 8.17 ± 2.31. The MPO activity in lung tissue increased from normal (1.35 ± 0.18) U / g lung tissue to 6 h (3.76 ± 0.89) U / g lung tissue. The lung tissue pathological damage was serious. However, anti-H4 antibody pretreatment can significantly antagonize lung injury. Conclusion Extracellular histones play an important protective role in the inflammatory injury of ALI.