The effect of resveratrol on lung and skin damage induced by belomycin in mice with systemic sclerosis

Abstract

Objective To figure out the effect of resveratrol (Res) in skin and lung pathology of systemic sclerosis (SSc) animal model and find a new target of anti-fibrosis therapy in SSc. Methods First, we established SSc animal model by daily subcutaneous injection of bleomycin (BLM) for 4 weeks in BALB/c mice. Then we fed the mice with Res. We observed the pathological changes in skin and lung and the expression of the deacetylase SIRT1. We observed the following parametrs. The pathologicalchanges in injected skin and lung which shown by hematoxylin-eosin (HE) staining, the expression of α-smooth muscle actin (α-SMA) in injected skin and lung which measured by immunohistochemistry, the expression of SIRT1 and pro-collagen Ⅲ mRNA which assessed by Real Time polymerase chain reaction (PCR). For the homosce dasticity data. We used oneway analysis of variance(ANOVA) and LSD-t test to compare between the groups. Results Daily subcutaneous injection of BLM for 4 weeks in Balb/c mice could successfully establish a mouse model of SSc. The thickening of skin and alveolar septum, the infiltration of inflammatory cells in lung, and even fibrosis insome area of lung could be observed. The number of α-SMA positive cells and the expression of pro-collagen Ⅲ mRNA were increased (P<0.05). Meanwhile, the expression of SIRT1 mRNA was decreased [the number of α-SMA positive cell: skin 26.4±5.9 vs 4.4±2.2, lung 14.6±4.6 vs 2.4±1.1, cells per view,P<0.01; the expres-sion of pro-collagen Ⅲ mRNA: 1.06±0.24 vs 0.45±0.14, relative to glyceraldehyde phosphate dehydrogenase (GAPDH), P<0.05]. Meanwhile, the expression of SIRT1 mRNA was decreased (1.01 ± 0.51 vs 5.03 ± 1.59, relative to GAPDH,P<0.05). Treated with Res, the pathological changes in skin and lung were alleviated and the number of α-SMA positive cells in lung and skin was decreased [skin 26.4±5.9 vs 10.0±3.5 (high dosage group), 26.4±5.9 vs 13.4±4.4 (medium dosage group); lung 14.6±4.6 vs 8.8±3.5 (high dosage group), cells per view, P<0.05]. There was were no significant differences in the expression of SIRT1 and pro-collagen Ⅲ mRNA in lung after treated by Res. Conclusion Daily subcutaneous injection of BLM for 4 weeks could successfully establish a mouse model of SSc. Res could be a new medicine for the treatment of SSc. Key words: Scleroderma, systemic; Bleomycin; Fibrosis; Resveratrol; SIRT1