Lutein Alleviate Acute Lung Injury Induced by Limb Ischemia-Reperfusion Through PPAR-γ/PI3K/AKT/NLRP3 Signaling

The detachment of cardiogenic emboli, the formation of arterial thrombosis, and the use of tourniquets in emergency situations of massive hemorrhage can all lead to acute limb ischemia. In order to save the limb, blood flow must be rapidly restored. However, the resulting ischemia reperfusion (IR) injury may trigger systemic inflammatory responses of varying degrees, and cause damage to distant organs. Acute lung injury (ALI) caused by acute limb IR (LIR) can significantly affect the prognosis of patients. Despite a large number of previous studies, there is currently no specific exists for this condition. This study aims to investigate the potential benefits of lutein on ALI caused by LIR (LIR-ALI). Network pharmacology analysis was used to predict the key targets and signaling pathways of lutein in the treatment of ALI. In addition, we established a mice model of LIR-ALI. Histological, ELISA, and Western blotting analyses were performed to determine the therapeutic effects and potential mechanisms of action. Our study found that lutein dose-dependently mitigated lung oxidative stress, inflammatory cell infiltration, and pyroptosis-related protein expression induced by LIR. The protective effect is partially mediated by regulating the PPAR-γ/PI3K-AKT/NLRP3 pathway to inhibit pyroptosis.