小剂量脂多糖气管内滴注制备急性肺损伤动物模型的探究

A Rat Model of Acute Lung Injury Induced by Lipopolysaccharide

目的 急性肺损伤/急性呼吸窘迫综合征 （Acute lung injury/Acute respiratory distress syndrome, ALI/ARDS） 发病率与死亡率均较高, 发病机制迄今尚不完全清楚, 也无特效的治疗方法.本实验成功地建立一种轻型ALI动物模型,为研究该病的早期发病机制及治疗提供重要的观察手段.方法 给予45只SD大鼠气管内灌注内毒素0.5 mL/kg （LPS 200 μg/mL）,观察4、12、24及48 h光镜和电镜下的病理改变;观察支气管肺泡灌洗液 （BALF） 中细胞分数、白蛋白等.结果 在观察时间内实验动物均存活.LPS给予后实验组病理检查发现①肺间质水肿;②肺泡腔内多形核中性粒细胞 （PMN） 浸润和红细胞渗出; ③肺泡Ⅰ型和Ⅱ型肺泡上皮细胞破坏.以LPS给予后4～12 h为最严重.BALF中PMN及白蛋白明显增加.结论 气管内灌注内毒素0.5 mL/kg （LPS 200 μg/mL） 成功地建立急性肺损伤动物模型.

Objective The Acute lung injury/acute respiratory distress syndrome （ALI/ARDS） has high morbidity and mortality. The mechanisms of both All and ARDS are still not fully elucidated. The purpose of this study was to establish a rat model of mild All, and to explore the mechanisms of All/ARDS. Methods There were 45 Spragne-Dawley rats weighing 250 ±20 g used in this experiment. Lipopolysaccharid （LPS） powder was reconstituted by sterile saline to a final concentration of 200μg/mL. 0.5 mL/kg LPS was instilled into the trachea via a needle. Lung tissue samples were taken at 4 h, 12 h, 24 h and 48 h after instillation of LPS, and histological examination by light and electron microcopy was performed. Bronchoalveolar lavage fluid （BALF） was collected to assess the presence of polymorphonuclear neutrophils （PMN） and albumin in BALF. Results All the rats survived during the experiment course. As compared to the control rats, the histological examination of LPS-treated group showed that ①pulmonary interstitial edema, ②PMN and erythrocyte were accumulated in alveoli lumen, ③The damages in both type Ⅰand Ⅱ epithelial cells were found. The pathological alterations above mentioned were more serious in LPS-treat rats at 4 - 12 h after LPS treatment. The amount of PMN and albumin in BALF was significantly increased. Conclusion An acute lung injury model of rats can be successfully established by instillation of 0.5 mL/kg （200 μg/mL） LPS into the trachea.