Protective Effect Of Glp-1 Analogue On Bleomycin-induced Pulmonary Fibrosis In Mice

Objective: The purpose of this study was to investigate the protective effect of Liraglutide,a glp-1 analogue,on bleomycin(BLM)-induced pulmonary fibrosis in mice,and its possible mechanism,providing a new theoretical basis for glp-1 analogue Liraglutide to become a drug for the treatment of pulmonary fibrosis.Methods: C57BL/6 male mice,weight about 20 g,a total of 30.The mice were randomly divided into 5 groups,6 mice in each group.The groups were as follows:(1).Blank group(daily subcutaneous injection of normal saline(200 m g/kg));(2).Liraglutide group(daily subcutaneous injection of Liraglutide(200 m g/kg));(3).BLM group(intraperitoneal injection of bleomycin solution(0.04mg/g)was given at day 0,4,7,10 and 14(d),respectively);(4).High dose of Liraglutide +BLM group(daily subcutaneous injection of Liraglutide(400mg/kg)+ intraperitoneal injection of bleomycin solution(0.04mg/g)was given at day 0,4,7,10 and 14(d).(5).Low dose of Liraglutide +BLM group(daily subcutaneous injection of Liraglutide(200mg/kg)+intraperitoneal injection of bleomycin solution(0.04mg/g)was given at day 0,4,7,10 and 14(d),respectively).During the experiment,the general conditions of body weight,activity degree and fur color of mice were monitored and recorded every day.On the 40 th day of the experiment,mice were taken out of the animal house,and lung tissue was taken from the mice after death.Then the following tests were performed:(1).The body weight of the mice and the lung weight of the mice were weighed and the lung coefficient was calculated.(2).Lung tissue samples were collected for Masson staining,and lung tissue structure changes and collagen deposition of mice in each group were observed and recorded under the microscope.(3).PT-PCR was used to detect the gene expression of GLP-1R in lung tissues of each group.(4).Western blotting : to test the protein expression of Collagen-1,TGF-?1,P-Smad2/3,T-Smad2/3,E-cadherin,?-SMA,GAPDH in each group in lung tissue.Results: The pulmonary fibrosis model was successfully constructed.Compared with BLM group,high dose of the Liraglutide peptide + BLM group and low dose of the Liraglutide peptide + BLM group mice showed less pulmonary fibrosis,GLP-1R gene expression increased and Collagen-1 ? smad2/3 protein expression decreased.And there was no statistical difference in the expression of pulmonary fibrosis,GLP-1R gene expression and Collagen-1?smad2/3 protein expression between the high dose of the Liraglutide peptide + BLM group and low dose of the Liraglutide peptide + BLM group.Conclusion: This study demonstrated that GLP-1 analogue had a protective effect on bleomycin-induced pulmonary fibrosis in mice.Glp-1 analogue may alleviate bleomycin-induced pulmonary fibrosis in mice by binding to GLP-1R and acting on TGF-?1/Smad signaling pathway.