[The Study of the Effect and Mechanism of Glucagon Like Peptide-1 in Bleomycin-induced Pulmonary Fibrosis in Mice].

OBJECTIVE: To investigate the potential value and mechanisms of glucagon like peptide-1 (GLP-1) on bleomycin (BLM)-induced pulmonary fibrosis in mice. METHODS: Mice were treated with a single sublethal dose of BLM (3 mg/kg ) via intratracheal infusion to produce pulmonary fibrosis, and then liraglutide (2 mg/kg) was given to the mice for 28 days by intraperitoneal injection. 28 days after BLM infusion, the number of total cells, macrophages and neutrophils, lymphocytes, and the content of transforming growth factor-beta 1 (TGF-ß1) in bronchoalveolar lavage fluid (BALF) were measured. Hematoxylin-eosin (HE) staining and Masson's trichrome (MT) staining were performed. The Ashcroft score and hydroxyproline content were analyzed. Real time(RT)-qPCR and Western blot were used to evaluate the expression of α-smooth muscle actin (α-SMA) and vascular cell adhesion molecule-1 (VCAM-1). The phosphorylation of nuclear factor-kappa B (NF-κB) p65 was also assessed by Western blot. DNA binding of NF-κB p65 was measured through TransAMTMNF-κB p65 transcription factor ELISA kit. RESULTS: GLP-1 reduced inflammatory cells infiltration and the content of TGF-ß1 in BLAF in mice with BLM injection. The Ashcroft score and hydroxyproline content were decreased by GLP-1 administration. Meanwhile, BLM-induced overexpression of α-SMA and VCAM-1 were blocked by GLP-1 treatment in mice. GLP-1 also reduced the ratio of phospho-NF-κB p65/total-NF-κB p65 and NF-κB p65 DNA binding activity in BLM-induced pulmonary fibrosis in mice. CONCLUSION: BLM-induced lung inflammation and pulmonary fibrosis were significantly alleviated by GLP-1 treatment in mice, possibly through inactivation of NF-κB.