The mechanisms of aldosterone antagonist on attenuating pulmonary fibrosis induced by bleomycin in the rats

Objective To investigate the mechanisms of aldosterone antagonist on attenuating pulmonary fibrosis in the rats.Methods The rats were randomly divided into control(group C),pulmonary fibrosis(group B)and spironolactone prevention groups(group T).Rat's pulmonary fibrosis was induced by endotracheal injection of bleomycin A_5.Then the rats received spironolactone(100mg·kg~(-1)·d~(-1))in group T or normal Saline(group B and C)by instilling into the stomach,six rats in each group were sacrificed on 7、14、28 days respectively after intratracheal instillation.Histological changes of the lungs were evaluated by HE staining and Masson's trichrome staining.Collagen content of the lung tissue was assessed by hydroxyproline(HYP)concentration.Transforming growth factor-β_1(TGF-β_1)level of plasma was measured by ELISA.Results①Aldosterone levels of plasma and tissue in group T and group B were significantly higher than those in group C(P＜0.05,P＜0.01)②HYP concentration of the lung in group T was lower than that in group B(P＜0.01);③Compared with group B,the grade of pulmonary fibrosis was significantly decreased in group T(P＜0.01);④TGF-β_1 concentration of plasma in group B at every time point was much higher than that in normal control and group T(P＜0.01).TGF-β_1 of plasma in group T was higher than that of control group at every time point,but was no significant difference(P＞0.05).The change of TGF-β_1 in the lung tissue was same as that of plasma;⑤The level of plasma aldosterone was positively related with the concentration of plasma TGF-β_1 in pulmonary fibrosis group:seven day(r=0.90, P＜0.05);fourteen day(r=0.94,P＜0.01);twenty-eight day(r=0.83,P＜0.05).Conclusions Spironolactone can attenuate pulmonary fibrosis in the rats,which may be through inhibiting the concentration of plasma TGF-β_1.