Effects Of Danshensu On TGF-β1/Smads Signaling Pathways In Rats With Pulmonary Fibrosis

Object:To investigate the effects of Danshensu on expression of TGF-β1,Smad3and Smad7mRNA in lung tissue of rats with bleomycin-induced pulmonary fibrosis,and to study the possible mechanism of Danshensu(DA) on pulmonary fibrosis in rats.Method:Pulmonary fibrosis was induced in SD rats by intratracheal instillation of bleomycin. Then the rats were injected intra-peritoneally with (dexamethasone1mg·kg-1·d-1(DXM group), DA15mg·kg-1·d-1(DA group), or physiological saline2ml·d-1(BLM group). Normal controls (NC group) received physiological saline both intratracheally and intraperitoneally. At28th day post-modeling, histological changes of the lungs were evaluated by hematoxylin-eosin (HE) stain and masson’s trichrome stain, the immunohistochemistry was used to detect the expressions of a-SMA in the rat lung tissues. TGF-β1, Smad3, Smad7mRNA expression were assessed by Real-time Quantitative Polymerase Chain Reaction (Real-time Q-PCR). Result:1. The result of pulmonary pathology:The level of alveolitis and fibrosis in group BLM was more serious than that in group NC on the28th day. These indicated that the model of pulmonary fibrosis established successfully. The levels of alveolitis and fibrosis in group DXM and group DA were less serious than that in group BLM; The levels of alveolitis and fibrosis in group DA were less seriousthan that in group DXM.2. The change of expression of a-SMA in lung tissue:Compared with NC group, the expression of a-SMA in lung tissue of rats in all the other groups were increased, there were significant differences on the28th day; Compared with BLM group, the expression of a-SMA in lung tissue of rats in group DXM was decreased,but there was no significant difference; Compared with BLM group, the expression of a-SMA in lung tissue of rats in group DA was decreased, there was significant difference; Compared with DXM group, the expression of a-SMA in lung tissue of rats in group DA was decreased, there was significant difference.3. The change of expression of TGF-β1and Smad3mRNA in lung tissue: Compared with NC group, the expression of TGF-β1and Smad3mRNA in lung tissue of rats in all the other groups were increased, there were significant differences on the28th day; Compared with BLM group, the expression of TGF-β1and Smad3mRNA in lung tissue of rats in group DXM and group DA were decreased, there were significant differences; Compared with DXM group, the expression of TGF-β1and Smad3mRNA in lung tissue of rats in group DA were decreased, there was significant difference.4. The change of expression of Smad7mRNA in lung tissue:Compared with NC group, the expression of Smad7mRNA in lung tissue of rats in all the other groups were decreased, there were significant differences on the28th day; Compared with BLM group, the expression of Smad7mRNA in lung tissue of rats in group DXM was increased, but there was no significant difference;Compared with BLM group, the expression of Smad7mRNA in lung tissue of rats in group DA was increased, there was significant difference; Compared with DXM group, the expression of Smad7mRNA in lung tissue of rats in group DA was increased, there was significant difference.Conclusion:1. DA can alleviate bleomycin-induced pulmonary fibrosis in rats, especially in the early stage.2. DA could inhibit the expression of TGF-β1, smad3and stimulate the expression of smad7in lung tissues, those effects might be involved in the important mechanism of DA against hepatic fibrosis.