Objective

The aim of this study was to investigate whether autophagy is enhanced in alveolar epithelial cells as well as its role in alveolar barrier function of in lipopolysaccharide (LPS)-induced ALI mice.

Materials and methods

Autophagy inhibitors, including 3-methyladenine (3-MA) and chloroquine (CLQ), and LPS were intraperitoneally administered to mice. Histological evaluation and confocal microscopy, Western blot, transmission electron microscopy, and ELISA were performed for analysis. First, the mouse model of ALI was established. Then, autophagy level changes in the mouse lung as well as the effects of autophagy inhibition on indirect ALI and alveolar epithelial barrier function induced by LPS were assessed. Finally, pro-inflammatory factors in BALF from ALI mice after autophagy inhibition by 3-MA or CLQ administration were detected.

Results

The experimental animal model of LPS-induced ALI had the expected features. In addition, autophagy in alveolar epithelial cells in ALI mice was enhanced. Furthermore, autophagy in alveolar epithelial cells promoted alveolar epithelial barrier dysfunction in LPS-induced ALI. Finally, autophagy inhibition resulted in reduced LPS-induced lung tissue inflammation.

Conclusion

These findings suggest that autophagy inhibition protects from alveolar barrier dysfunction in LPS-induced ALI mice by targeting alveolar epithelial cells.

中文翻译：

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自噬抑制通过靶向肺泡上皮细胞来防止 LPS 诱导的 ALI 小鼠的肺泡屏障功能障碍。

客观的

本研究的目的是研究自噬是否在肺泡上皮细胞中增强，及其在脂多糖 (LPS) 诱导的 ALI 小鼠肺泡屏障功能中的作用。

材料和方法

自噬抑制剂，包括 3-甲基腺嘌呤 (3-MA) 和氯喹 (CLQ)，以及 LPS 被腹腔注射给小鼠。进行组织学评估和共聚焦显微镜检查、蛋白质印迹、透射电子显微镜检查和 ELISA 进行分析。首先，建立了ALI的小鼠模型。然后，评估了小鼠肺中自噬水平的变化以及自噬抑制对 LPS 诱导的间接 ALI 和肺泡上皮屏障功能的影响。最后，检测到 3-MA 或 CLQ 抑制自噬后 ALI 小鼠 BALF 中的促炎因子。

结果

LPS诱导ALI的实验动物模型具有预期的特征。此外，ALI 小鼠肺泡上皮细胞的自噬增强。此外，肺泡上皮细胞中的自噬促进了 LPS 诱导的 ALI 中的肺泡上皮屏障功能障碍。最后，自噬抑制导致 LPS 诱导的肺组织炎症减少。

结论

这些发现表明，自噬抑制通过靶向肺泡上皮细胞来防止 LPS 诱导的 ALI 小鼠的肺泡屏障功能障碍。