Effect of spironolactone on pulmonary fibrosis caused by paraquat poisoning in rats and study of its mechanism

Objective To observe whether spironolactone would ameliorate pulmonary fibrosis caused by paraquat(PQ) poisoning in rats and explore its possible mechanism.Methods Fifty-four male SD rats were randomly divided into control group,PQ group treated intragastrically with PQ 80 mg/kg,and PQ+SPI group treated intragastrically with PQ 80 mg/kg and received spironolactone 100 mg/kg once a day.The rats in each group were sacrificed and the lungs were harvested on each 7,14 or 28 days respectively.Pulmonary coefficient in each group was calculated.Histological changes of lungs and the scores of pulmonary alveolitis and fibrosis were evaluated by HE staining and Masson Staining.Aldosterone(ALD)levels of plasma and lung tissue were detected.Hydroxyproline concentration were detected and the expressions of transforming growth factor-beta 1(TGF-β1) and alpha-smooth muscle actin(α-SMA) in lung tissue were assessed by immunohistochemistry.Results Aldosterone levels of plasma and lung tissue in PQ group and PQ+SPI group were markedly higher than those in control group,and there was significant difference on 14 d and 28 d(P0.05).The scores of pulmonary alveolitis and fibrosis,pulmonary coefficient and HYP concentration in PQ+SPI group were significantly lower than those in PQ group(P0.01);The protein expression of TGF-β1 and α-SMA in lung tissue in PQ+SPI group on 14 d and 28 d were significantly lower than those in PQ group (P0.05 or P0.01).Conclusion ALD,TGF-β1 and α-SMA may play an important role in the development of pulmonary fibrosis caused by PQ poisoning.Spironolactone can alleviate paraquat-induced pulmonary fibrosis,which may be due to inhibition of aldosterone receptor and,in part,be associated with reduction in TGF-β1 and α-SMA.