Abstract
Smoking and infection are the most common risk factors for acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Irisin is a hormone-like substance that helps reduce oxidative stress and inflammation in lung diseases. This study aims to explore the potential regulatory mechanism of irisin in AECOPD induced by CSE combined with LPS. Autophagy-deficient models were established in mice and MH-S cells. Pathological changes in mouse lung tissues were assessed using HE staining, while Irisin expression was detected via immunofluorescence. Levels of IL-1β, IL-6, and TNF-α in mouse BALF and MH-S cell supernatants were measured by ELISA. Autophagic flux in MH-S cells was monitored using the Ad-mCherry-GFP-LC3B dual-fluorescence system and transmission electron microscopy. Western blotting was performed to analyze autophagy-related proteins in mice and MH-S cells, elucidating the molecular mechanism of Irisin's protective effects. Irisin can reduce the accumulation of the autophagy marker protein P62 and promote the conversion of LC3-I to LC3-II through the AMPK-Beclin1 pathway, increase autophagosome-lysosome formation, effectively restore damaged autophagic flux, and lower the levels of pro-inflammatory factors IL-1β, IL-6, and TNF-α elevated by CSE + LPS. Irisin activates protective autophagy through the AMPK-Beclin1 pathway, restores the autophagy imbalance induced by CSE + LPS in the lungs, reduces lung inflammation levels, and provides a new therapeutic target for the treatment of AECOPD.