Objective To improve the success rate of ARDS disease model, we explored the optimal condition for constructing the model through endotracheal instillation of LPS, eventually providing a technical support for the basic research of ARDS. Methods A total of 116 C57 / BL6N mice were included in this research.We explored the optimal administration conditions by comparing the drug distribution and actual modeling effects of different body positions ( slant position, supine position) and LPS volumes ( 30 μL / 20 g, 60 μL / 20 g, 90 μL / 20 g ) . Further, different anesthesia methods were compared according to the physiopathological status of mice. The above optimized conditions were validated by ARDS modeling. Results Compared to the supine position, LPS instilling to mice in a slant position can distribute more evenly across lung lobes. A dosage of 60 μL LPS / 20 g body weight can meet the modeling requirement, such as thickening of alveolar walls and increasing of neutrophils according to  H&E staining. Compared to the control group, significant differences were observed in injury score,vascular permeability and systemic inflammation(P<0. 001) . Last but not least, intraperitoneal injection of anesthesia exacerbates inflammation in mice and affects blood oxygen saturation ( P < 0. 01 ) .Conclusion C57 / BL6N male mice (6-8 weeks old, 20 g body weight) were used for establishing an ARDS disease model. Isoflurane inhalation anesthesia was selected before surgery, which was performed in a slant position. The optimal volume of LPS was 60 μL / 20 g ( body weight) for inducing ARDS. Tribromoethanol by intraperitoneal injection was not recommended for anesthesia, due to side effects such as extra inflammatory burden and reduction of blood oxygen saturation.

:acute respiratory distress syndrome, animal model, model optimization

目的 探索暴露式气管内滴注脂多糖( LPS)构建急性呼吸窘迫综合征( ARDS) 疾病模型的最优条件,提高造模成功率,优化模型,为 ARDS 的基础研究提供技术支撑。 方法共 116 只 C57 / BL6N 小鼠纳入本次实验。 作者通过比较不同给药体位(斜卧位、平卧位)及给药体积(30、60 、90 μL / 20 g) 的药物分布情况及实际造模效果,探索最佳给药条件。 进而通过比较不同麻醉方式对小鼠造模及生理状态的影响选择最佳麻醉方式。 通过 ARDS 造模对上述优化条件进行验证。 结果 斜卧位给药相较于平卧位给药能够使药物更均匀的分布于各个肺叶。 60 μL / 20 g 给药体积能够满足造模需求,在 H&E 染色上能够观察到肺泡壁增厚以及大量中性粒细胞聚集,损伤评分与对照组相比具有明显统计学差异(P<0. 001) ,且在血管通透性及全身炎症等方面均有明显差异。 腹腔注射麻醉加重小鼠炎症状态,影响血氧饱和度(P<0. 01) 。 结论推荐选择体质量约为 20 g 的 6 ~ 8 周龄小鼠作为建立 ARDS 疾病模型对象,术前使用异氟烷吸入麻醉,以斜卧位进行手术,术中推荐给药体积为 60 μL / 20 g。 三溴乙醇腹腔注射麻醉加重小鼠除 LPS 外的炎症负担,降低小鼠血氧饱和度,不推荐使用。

急性呼吸窘迫综合征, 动物模型, 模型优化