Objective To study the role of Nrf2/GPX4 signaling pathway in irisin alleviating lipopoly-saccharide (LPS)-induced acute lung injury in rats.

Method  Seventy-two healthy male SD rats were ran-domly divided into control group (C group), acute lung injury group (ALI group), irisin group (Ir group), irisin+Nrf2 inhibitor group (Ir+ML385 group). 24 hours after the model preparation, bronchoalveolar lavage fluid (BALF) was collected for protein concentration determination, and the contents of IL-6 and TNF-α in BALF were detected by ELISA. Pathologic results of lung tissue sections were observed by HE staining and scored, and the wet/dry weight ratio of the lung tissue was calculated. The contents of Fe²⁺, MDA and GSH in lung tissue homogenate were detected by colorimetric method. The protein levels of GPX4, ACSL4 and nuclear Nrf2 in lung tissues were determined by western blot (WB).

Result  Compared with the control group, the protein contents in BALF, the IL-6 and TNF-α contents, lung pathological in-jury score, wet/dry weight ratio, the contents of Fe²⁺ and MDA were increased, the GSH content and GPX4 level were decreased, the protein levels of ACSL4 and nuclear Nrf2 were increased in ALI group (P<0.05). Compared with the ALI group, the protein contents in BALF, the IL-6 and TNF-α contents, lung patho-logical injury score, wet/dry weight ratio, Fe²⁺ and MDA contents were decreased, the GSH content as well as the protein levels of GPX4 and nuclear Nrf2 were increased, ACSL4 level was decreased in Ir group (P<0.05). Compared with the Ir group, the protein contents in BALF, the IL-6 and TNF-α contents, lung pathological injury score, wet/dry weight ratio, Fe²⁺ and MDA contents were increased, the GSH content as well as the protein levels of GPX4 and nuclear Nrf2 were decreased, ACSL4 level was increased in the Ir+ML385 group (P<0.05).

Conclusion  Nrf2/GPX4 signaling pathway is involved in irisin alleviating LPS-induced acute lung injury in rats, which is associated with the inhibition of ferroptosis.

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