Quercetin Regulates Macrophage Polarization Via the PI3K/Akt Signaling Pathway and Improves Stenosis after Tracheal Injury

Objective This study investigates how quercetin improves tracheal stenosis by modulating macrophage polarization via the PI3K/Akt signaling pathway. Methods Rabbits were divided into five groups to establish a tracheal stenosis model. Immunofluorescence was used to detect α-SMA protein in the tracheal mucosa of each group. Quercetin was applied to RAW264.7 macrophages, and morphological changes were observed using HE staining. Flow cytometry was used to assess the M1/M2 macrophage ratio. M1 and M2 macrophages were co-cultured with fibroblasts, and α-SMA mRNA levels were measured using Real-time PCR. Additionally, RAW264.7 cells were treated with a PI3K inhibitor and quercetin to analyze the PI3K/Akt signaling pathway and M1/M2 markers through Real-time PCR. Results Quercetin treatment reduced α-SMA expression in the tracheal mucosa. The morphological changes in RAW264.7 cells post-quercetin intervention resembled those induced by IL4. The M2/M1 ratio in RAW264.7 cells approached 1.0. Quercetin decreased iNOS and TNF-a expression while up-regulating Arg1 and IL10 in RAW264.7 cells. In tracheal stenosis tissue, Akt1 and Akt3 levels increased, whereas Akt2 decreased. Quercetin up-regulated Akt2 and Akt3 and down-regulated Akt1. Following PI3K inhibitor intervention, Akt1 and Akt3 increased, and Akt2 decreased; however, quercetin did not reduce Akt1 but maintained Akt2 and Akt3 upregulation. The PI3K inhibitor up-regulated iNOS expression, which quercetin subsequently down-regulated. Conversely, Arg1 was down-regulated by the PI3K inhibitor and up-regulated by quercetin. When M1 and M2 macrophages were co-cultured with fibroblasts in equal proportions, α-SMA mRNA expression was down-regulated. Conclusion Quercetin enhances tracheal stenosis improvement by regulating macrophage polarization through the PI3K/Akt signaling pathway.