Effect of Losartan on Bleomycin-Induced Pulmonary Fibrosis of Rat,and Its Mechanisms

Objective: To investigate the effect of losartan,an antagonist of angiotensin Ⅱ type 1 receptor,on the bleomycin-inducesd pulmonary fibrosis in rats and the expression of transforming growth factor-beta(TGF-β) and hepatocyte growth factor(HGF) in rat's lung and to explore the mechanisms.Methods: Forty-five Wistar rats were divided into the losartan,model and control groups.In the losartan group,the pulmonary fibrosis was induced by intratracheal instillation of bleomycin(BLM),and then received losartan 10 mg/kg per day orally.In the model group,all rats received normal saline orally after pulmonary fibrosis was induced.In the control group,all rats only received normal saline orally and intratracheally.Five rats in each group were killed 7,14 and 28 days after intratracheal instillation.Collagen content of the lung tissue was assessed by hydroxyproline concentration.Histological changes of lungs were evaluated by Massons trichrome stain.The expressions of TGF-β and HGF proteins in lung were determined by semi-quantitative PCR.Results: Hydroxyproline concentration in model and losartan group was higher than that in control group on the 7th,14th and 28th day after treatment(P0.05).TGF-β expression level in model group was higher than that in control group,and HGF protein in model group was higher than that in control group on the 7th day after treatment and lower than that in control group on the 14th and 28th day respectively(all P0.05).TGF-β expression level in losartan group was lower than that in group model on the 14th and 28th day respectively,and HGF expression level in losartan group was higher than that in group model on the 7th,14th and 28th day respectively(all P0.05).Conclusion: Losartan alleviates BLM-induced pulmonary fibrosis in rats by inhibiting the expressions of TGF-β and stimulating the expression of HGF in lung.