Resveratrol alleviates bleomycin-induced pulmonary fibrosis by inhibiting epithelial-mesenchymal transition and down-regulating TLR4/NF-κB and TGF-β1/smad3 signalling pathways in rats

Background: Pulmonary fibrosis (PF) is a difficult clinical condition with no effective treatment and a high mortality rate. Patients usually die of respiratory failure. In the present, we hypothesized that resveratrol (Res) could suppress bleomycin (BLM)-induced PF in rats and examined the detailed mechanism.

Methods: The successfully established BLM-induced PF rat models and normal healthy rats were randomly assigned into the control, model, Res-low, Res-medium, and Res-high groups. The extent of PF in rats was determined by Masson and H&E staining. ELISA was used to detect changes in the inflammatory factors IL-1β, IL-6, TNF-α, SOD, and GSH-PX in lung tissue. Microscopic lung fibrosis scoring was done using the Ashcroft scale. Western blotting and RT-qPCR assays were used to analyze the effects of Res on the epithelial-mesenchymal transition (EMT).

Results: The administration of Res ameliorated the BLM-induced PF in vivo. Res could inhibit pro-inflammatory factors and regulates oxidative stress levels. It also revealed that Res downregulated Vimentin and upregulated E-cadherin expression. Res inhibited fibrosis and inflammatory responses in rat lung tissue. The activation of the TLR4/NF-κB and TGF-β1/smad3 signaling pathways were inhibited following Res treatment.

Conclusion: The present study suggested that Res may protect against BLM-induced PF by inhibiting the EMT and down-regulating the TLR4/NF-κB and TGF-β1/smad3 signaling pathways.