Intervention effect and mechanism of polyguanylic acid on pulmonary fibrosis in silica-exposed rats / 中国职业医学

ABSTRACT

OBJECTIVE: To observe the intervention effect of polyguanylic acid( Poly G) on silicosis fibrosis in rats and to explore its possible mechanism. METHODS: Specific pathogen free adult male SD rats were randomly divided into 6 groupscontrol group,silicosis model group and 4 intervention groups( intervention group 1,2,3 and 4),with 5 rats in each group. Except for the control group,the other 5 groups were treated with 1. 0 m L silica suspension( 50. 0 g / L mass concentration) by intratracheal intubation,four intervention group was given by intraperitoneal injection of 1,2,3 and 4doses of Poly G at 2. 5 mg / kg body weight after establishing the model for 1 to 21 days. All rats were sacrificed 28 days after silicosis model establishment. Lung pathological changes were observed and the pulmonary fibrosis was evaluated by Ashcroft scores. The expression of Macrophage receptor with collagenous structure( MARCO),transforming growth factor-β1( TGF-β1),E-cadherin,Vimentin and α-smooth muscle actin( α-SMA) protein were detected by western blot.RESULTS: In the model group,a large number of dust cell aggregates were found in the alveolar cavity and diffuse collagen deposition appeared in the pulmonary interstitial,indicating that silicosis model was successfully constructed. The alveolar structure of the single dose intervention group was integral and the degree of fibrosis was significantly less than that of the silicosis model group. Compared with the control group,MARCO,TGF-β1,Vimentin and α-SMA expression levels of silicosis model group were increased,the expression level of E-cadherin decreased, the difference was statistically significant( P < 0. 05). Compared with the silicosis model group,TGF-β1,Vimentin and α-SMA expression levels of single dose intervention group decreased,E-cadherin expression level increased,the difference was statistically significant( P < 0. 05). The dose-response relationship could not perceived between the Poly G intervention times and the Ashcroft scores or the protein expression levels of MARCO,TGF-β1,E-cadherin,Vimentin and α-SMA respectively. CONCLUSION: Poly G can effectively reduce lung inflammation and fibrosis in rats. The effect of single dose intervention( 2. 5 mg / kg body weight,intraperitoneal injection) at the first day after silica exposure is the best. The mechanism of action may be related to the low-does Ply G which can inhibit the epithelial-mesenchymal transition and then result in the decrease of collagen synthesis.