胸部撞击伤复合脂多糖致急性肺损伤大鼠模型的建立

摘要

目的：建立SD（Sprague Dawley）大鼠经胸部撞击复合内毒素所致急性肺损伤（ALI）模型，为后续ALI的救治和发病机制研究提供支撑。方法采用BMI-Ⅲ型生物撞击机，对SD大鼠行右侧胸部准静态正面撞击，比较动物受撞击后的呼吸及伤后24h肺部大体伤情。确认25kPa为合适的驱动压力后，于撞击后即刻通过尾静脉分别注射10、15、20mg/kg 3种剂量脂多糖（LPS），观察伤后动物的死亡率及肺损伤病理情况。结果250kPa所致肺损伤伤情中度，动物无死亡。撞击后即刻复合LPS的3种剂量中，20mg/kg可致动物48h死亡率为80％，10mg/kg 则致动物48h死亡率仅20％，15mg/kg 致动物48h 死亡率为70％。250kPa＋15mg/kg条件下的肺组织病理检测可见撞击区旁红细胞、炎细胞聚集，肺泡腔及肺泡间隔出现粉红色液体，肺泡间隔增厚等ALI典型病变。结论以250kPa驱动压力行右侧胸部撞击复合15mg/kg的LPS静脉注射，既保证伤情达到一定严重程度，又保证后续能得到有效的治疗观察结果，为最佳致伤条件。所建立的大鼠ALI动物模型操作简便，致伤参数可控，且重复性好，病变典型，可作为研究急性肺损伤较理想的实验动物模型。%Objective To establish an animal model of acute lung injury ( ALI) following chest impact combined with lipopolysaccharide ( LPS) challenge .Methods The lung injury of rats was caused by the BMI-Ⅲbiological impact device on right lung at quasi-static pattern .Using 250 kPa as a suitable driving pressure ,the chest injured rats were injected with 10,15,20 mg/kg LPS via tail vein respectively .The outcome of the ALI rats was ob-served.Results The driving pressure of 250 kPa induced moderate lung injury ,no animal died after experiment . The mortality of chest injury rats with 20mg/kg of LPS was 80% within 48 hours,70% with 15mg/kg of LPS,and 20%with 10mg/kg of LPS.We set up the ALI model by 250 kPa driving pressure combined with 15mg/kg LPS. The biopsy features of the lungs demonstrated typical pathological changes after ALI .Conclusion 250 kPa driving pressure combined with 15mg/kg LPS is an ideal injury condition for ensuring a successful injury model .The estab-lished model of ALI is relatively simple ,easily controllable and highly repeatable ,which can be used as a feasible model for the study of ALI .