Rapamycin in rat model of bleomycin-induced pulmonary fibrosis and its impact on expression of transforming growth factorial

Abstract

Objective To study the effect of rapamycin on bleomycin induced pulmonary fibrosis in rats and its possible mechanism. Methods One bundrad and fifty SD rats were randomly divided into three groups. In the rapamycin group and the model group, pulmonary fibrosis was induced by intratracheal instillation of bleomycin,and then the former group received rapamycin 0.5 mg/kg daily, but the latter group received oral normal saline. In the control group, normal saline was given both intratracheally and orally. Ten rats in each group were sacrificed on the 3rd,7th, 14th,28th,and 56th day after intratracheal instillation. Histological changes of the lungs were evaluated by HE stain, Masson＇s trichrome stain, and sirius red stain. Hydroxyproline content of the lung tissue was assessed by hydroxyproline concentration. The mRNA expression of transforming growth factor β1 （TGF-β1） was detected by reverse transcription-polymerase chain reaction. TGF-β1 protein expression in lung tissue was assessed by immunobistochemistry. Results The lung hydroxyproline content and alveolitis in the model group were higher than those in the control group at each time point,the degree of pulmonary fibrosis in the model group was higher than that in the control group on the 14th,28th and 56th day （ P〈0.05）. The content of hydroxyproline in lung tissue in the rapamycin group was lower than that in the model group on the 14th,28th and 56th day,alveolitis in the rapamycin group was lower than that in the model group on the 14th and 28th day,the degree of pulmonary fibrosis in the rapamycin group was lower than that inthe model group on the 28th and 56th day （ P〈0.05）. The expression of TGF-β1 mRNA in the model group was higher than that in the control group on the 3rd, 7th, 14th and 28th day, the expression of TGF-β1 mRNA in the rapamycin group was lower than that in the model group on the 7th and 14th day （P〈0.05）. Conclusions Rapamycin alleviates bleomycin-induced pulmonary fibrosis in rats. Inhibiting the expressions of TGF-β1 in lung tissues may be one of the mechanisms. Key words: Pulmonary fibrosis ; Bleomycin; Rapamycin; Transforming growth factor-β1