Liraglutide alleviates sepsis-induced acute lung injury by regulating pulmonary surfactant through inhibiting autophagy

Abstract

Background

Pulmonary surfactant (PS) plays an important role in the treatment of sepsis-induced acute lung injury (ALI). Liraglutide, a glucagon-like peptide-1 (GLP-1) analog, improves the secretion and function of PS in ALI, but the underlying mechanism remains unknown. This study aimed to investigate how liraglutide regulates PS secretion in ALI.

Methods

C57BL/6 mice were injected subcutaneously with normal saline containing different concentrations of liraglutide after the establishment of the ALI model. MLE-12 cells were treated with liraglutide after LPS stimulation. The survival rate of mice, wet/dry weight ratio, inflammatory factors in bronchoalveolar lavage fluid (BALF), pulmonary injury, and apoptosis were analyzed. Cell viability, proliferation, apoptosis, the expression of SP-A, SP-B, and expression of autophagy-related proteins in cells were measured.

Results

ALI mice showed reduced pulmonary injury, less apoptosis, and less inflammation compared to the controls. Liraglutide prolonged survival, decreased the wet/dry weight ratio, reduced inflammatory responses, and attenuated pulmonary edema compared with the ALI group. Moreover, LPS-induced cell damage and reduction of SP-A and SP-B expression were markedly reversed by liraglutide in MLE-12 cells. Furthermore, the protective effects of liraglutide were reversed by rapamycin.

Conclusion

Liraglutide alleviate sepsis-induced ALI by inhibiting autophagy and regulating PS.

Keywords:

• Liraglutide
• sepsis
• acute lung injury
• pulmonary surfactant
• autophagy

Author contributions

L.W. and W.C. conceived and planned the study; J.G. wrote the manuscript; X.Z. and R.P. performed the experiments; Y.Z. analyzed the data. All authors have read and approved the final version of the manuscript.

Disclosure statement

The authors declare that they have no competing interest with the contents of this article.

Availability of data and material

All data generated or analyzed during this study are included in this published article.

Additional information

Funding

This study is supported in part by Zhejiang Provincial Natural Science Foundation of China under (Grant No. LTGD23H150001), the Research Fund of Zhejiang Provincial People’s Hospital (ZRY2019C002), General Scientific Research Project of Zhejiang Provincial Department of Education (Grant No. Y202249327), and the Medical and Health Research Project of Zhejiang Province (Grant No. 2023KY212).