中性粒细胞活化在海水淹溺致肺损伤中的作用

Role of neutrophil activation in acute lung injury induced by seawater drowning

目的 探讨中性粒细胞活化在海水淹溺致肺损伤中的作用.方法 36只新西兰兔随机分成6组：0（对照）、1、3、6、12、24 h组,每组6只动物.海水组经气管插管灌注2 mL/kg海水.观察不同时间点血气分析和支气管肺泡灌洗液（BALF）中性粒细胞计数及百分比的变化,计算肺通透指数（LPI）;以生化法检测髓过氧化物酶（MPO）、丙二醛（MDA）含量,以酶联免疫吸附法（ELISA）分析中性粒细胞弹性蛋白酶（NE）活性,同时进行病理学检查,并计算肺病理评分（LPS）.结果灌注海水后氧合指数迅速低至300 mm Hg 以下,持续时间长达6 h（P〈0.01）.肺大体标本以灌注后3 h瘀血水肿最严重,体积最大.显微镜下炎症细胞浸润以6~12 h最突出,肺泡间隔宽度随时间延长而加重.各时间点BALF中性粒细胞计数及百分比,肺组织NE、MPO、MDA含量,LPI及LPS均显著高于对照组（P〈0.05或P〈0.01）,多于3~12 h达高峰.各指标间均有显著相关性（P〈0.05或P〈0.01）.结论 中性粒细胞是SWD-ALI早期主要的炎症效应细胞,氧化应激反应与NE释放协同参与了肺组织损伤.中性粒细胞募集和活化在SWD-ALI发生发展中起重要作用.

Objective To explore the role of neutrophil activation in pathogenesis of acute lung injury induced by seawater drowning （ SWD - ALl ） in rabbit model. Methods Thirty - six New Zealand rabbits were divided randomly into 6 groups ： control group （ 0 h ） and 5 seawater drowning groups （S 1 h, S 3 h, S 6 h, S 12 h, S 24 h）. There were 6 rabbits at each group. The drowning model was established by pouring seawater （2 mg/kg） into tracheal catheter. Blood gas analysis and the eount and proportion of neutrophil in bronchoalveolar lavage fluid （BALF） were observed at different time. Lung permeability index （ LPI ） was calculated. The contents of myeloperoxidase （ MPO ） and maleic dialdehyde （MDA） were measured by biochemical method. The concentrations of neutrophil elastase （NE） was detected by means of enzyme - linked immunosorbent assays （ELISA）. At the same time, the changes of pathology were shown by hematoxylin -eosin （HE） staining and lung pathologic scores （LPS） were measured. Results After pouting seawater, oxygenation index （PaO2/FiO2） fell to （203.76 ±37. 8） mm Hg at 0. 5 h and did not elevate to more than 300 mm Hg until 6 h. The lung specimen of S 3 h group had the largest volume and the most manifest edema and congestion. Furthermore, the histopathologie findings indicated that pulmonary sepatal thickened in time dependence and inflammatory cell infiltration was most massive at 6 - 12 h. The count and proportion of neutrophil in BALF, the contents of MPO, MDA and NE in lung tissue, LPI and LPS at each seawater drowning group were all higher than those in control group （P 〈0. 05 or P 〈0. 01 ）. ALL the parameters climbed to the top at 3 ~ 12 h and correlated well with each other （ P 〈 0. 05 or P 〈 0. 01 ）. Conclusion Neutrophil may be the most inflammatory cell in early SWD -ALl. Oxidative stress reaction and release of NE are all involved in the pathogenesis of SWD - ALI in cooperative method. The recruitment and activation ofneutrophil may play an important role in the development of SWD - ALI.