Effects of astragalus polysaccharide on paraquat-induced pulmonary fibrosis in rats by regulating TGF-β1/Smads signaling pathway / 西安交通大学学报(医学版)

ABSTRACT

Objective To explore the effects of astragalus polysaccharide on paraquat-induced pulmonary fibrosis in rats by regulating TGF-β1/Smads signaling pathway. Methods Rats were divided into control group, APS, PQ and PQ + APS groups. Paraquat was used to establish the rat model of pulmonary fibrosis. Lung wet/dry weight ratio and hydroxyproline content were measured; the pathological changes were observed by HE staining. The fibrosis in lung tissues was observed by Masson staining, and the concentrations of tumor necrosis factor α(TNF-α), interleukin 1β(IL-1β), and IL-6 were measured by ELISA kits. RT-PCR was used to detect the gene expressions of transforming growth factor-β1 (TGF-β1), collagen Ⅰ and collagen Ⅲ. Western blotting was used to detect the protein expressions of E-cadherin, α-smooth muscle actin (α-SMA), Vimentin, TGF-β1, Smad3, p-Smad3, and Smad7. Results Compared with the control group, in the PQ group the lung wet weight/dry weight ratio increased (t=12.922, P<0.001) and the hydroxyproline content increased (t=20.920, P<0.001). There were pathological changes and collagen deposition in lung tissues. TNF-α (t=23.932, P<0.001), IL-1β (t=34.826, P<0.001), and IL-6 (t=17.985, P<0.001) in alveolar lavage fluid all increased in concentration. TGF-β1 (t=20.934, P<0.001), collagen Ⅰ (t=26.853, P<0.001), and collagen Ⅲ (t=18.493, P<0.001) gene expressions increased. E-cadherin (t=25.456, P<0.001) protein expression decreased; α-SMA (t=26.980, P<0.001), Vimentin (t=23.862, P<0.001), and TGF-β1 (t=39.836, P<0.001) protein expressions increased. p-Smad3/Smad3 ratio (t=19.606, P<0.001) increased, Smad7 (t=30.904, P<0.001) protein expression decreased. Compared with PQ group, in PQ+APS group lung wet weight/dry weight ratio decreased (t=9.174, P<0.001), hydroxyl amino acid content (t=10.999, P<0.001) decreased, and lung tissue pathology and collagen deposition reduced. TNF-α (t=8.654, P<0.001), IL-1β (t=18.164, P<0.001), and IL-6 (t=7.573, P<0.001) concentrations in alveolar lavage fluid decreased. TGF-β1 (t=8.879, P<0.001), collagen Ⅰ (t=12.687, P<0.001) and collagen Ⅲ (t=11.333, P<0.001) gene expressions reduced. E-cadherin (t=14.255, P<0.001) protein expression increased; α-SMA (t=16.866, P<0.001), Vimentin (t=18.439, P<0.001), and TGF-β1 (t=14.688, P<0.001) protein expressions as well as p-Smad3/Smad3 ratio (t=11.384, P<0.001) were down-regulated; Smad7 (t=13.131, P<0.001) protein expression increased. Conclusion Astragalus polysaccharide can alleviate paraquat-induced pulmonary fibrosis in rats. Its mechanism may be related to inhibiting the TGF-β1/Smads signal pathway.