Protective mechanism of Irisin in sepsis-induced acute lung injury

  AIM  To explore the mechanism of Irisin in sepsis-induced acute lung injury (ALI).

  METHODS  C57 mice were randomly divided into Con group, Irisin group, CLP Group and CLP-Irisin group. A549 cells were divided into Con group, LPS group, Irisin group (LPS-Irisin), LPS-Irisin-UA group, LPS-UA group and 3-MA group. CCK-8 kit was used to detect cell viability, MPO, PaO₂/FiO₂, IL-1α, IL-6, TNF-α, H₂O₂, MDA and GSH-Px activity and Western blot was used to analyze the expression of mitophagy related proteins.

  RESULTS  In vivo studies showed that Irisin alleviated sepsis-induced ALI by regulating mitophagy and reducing the expression of inflammatory factors in lung tissues (P<0.05). Meanwhile, the oxygen index was increased and the mortality rate of mice was decreased. In addition, Irisin resisted CLP-induced ALI by reducing oxidative stress (P<0.05). In vitro studies confirmed that LPS significantly reduced the viability of A549 cells and increased the expression of inflammatory factors and abnormal mitophagy (P<0.05). Irisin or 3-MA treatment significantly reduced LPS induced cell injury and UA treatment partially counteracted the protective effect of Irisin on A549 cells (P<0.05).

  CONCLUSION  Irisin alleviates sepsis-induced ALI by regulating Pink1/Parkin mediated mitophagy and maintaining mitochondrial functions.