Sevoflurane anesthesia ameliorates LPS-induced acute lung injury (ALI) by modulating a novel LncRNA LINC00839/miR-223/NLRP3 axis

BMC Pulmonary Medicine

Xiuying Wu¹  Zhiling Fu¹  Yan Zhang¹  Fushuang Zheng² 

[1] Department of Anesthesiology, Shengjing Hospital of China Medical University;Department of Thoracic Surgery, Shengjing Hospital of China Medical University;

关键词: Acute lung injury;    Sevoflurane;    LINC00839;    miR-223;    NLRP3;    Pyroptosis;   

DOI  :  10.1186/s12890-022-01957-5

来源: DOAJ

【 摘 要 】

Abstract Background Sevoflurane is considered as a lung-protective factor in acute lung injury (ALI), but the underlying molecular mechanism remains largely unknown. The present study identified for the first time that sevoflurane ameliorated lipopolysaccharide (LPS)-induced ALI through regulating a novel long non-coding RNA LINC00839, and uncovered its regulatory mechanism. Methods LPS-induced ALI models were established in mice or mouse pulmonary microvascular endothelial cells (MPVECs), and they were administered with sevoflurane. Real-Time quantitative PCR, western blot and bioinformatics analysis were performed to screen the aberrantly expressed long non-coding RNA and the downstream molecules in sevoflurane-treated ALI models, and their roles in the protection effect of sevoflurane were verified by functional recovery experiments. Results Sevoflurane relieved LPS-induced lung injury, cell pyroptosis and inflammation in vitro and in vivo. LINC00839 was significantly suppressed by sevoflurane, and overexpression of LINC00839 abrogated the protective effects of sevoflurane on LPS-treated MPVECs. Mechanismly, LINC00839 positively regulated NOD-like receptor protein 3 (NLRP3) via sequestering miR-223. MiR-223 inhibitor reversed the inhibitory effects of LINC00839 knockdown on NLRP3-mediated pyroptosis in LPS-treated MPVECs. Furthermore, both miR-223 ablation and NLRP3 overexpression abrogated the protective effects of sevoflurane on LPS-treated MPVECs. Conclusion In general, our work illustrates that sevoflurane regulates the LINC00839/miR-223/NLRP3 axis to ameliorate LPS-induced ALI, which might provide a novel promising candidate for the prevention of ALI.

【 授权许可】

Unknown