Establishment Of Resveratrol In Animal Models Of Systemic Sclerosis Its Role In Lung And Skin Lesions

Background:Systemic sclerosis (SSc) is a connective tissue disease which can involve many organs. The fibrosis of skin and lung is one of the most important manifestations of SSc, which represented by proliferation of myofibroblasts and the abnormal deposition of extracellular matrix (ECM) components. By now there is few effective therapy for pulmonary fibrosis in patients with SSc, which leads to poor prognosis. SIRT1, one of the hi stone deacetylases (HDACs) may take part in the pathological process of fibrosis in SSc through the transforming growth factor-p (TGF-p) induced signal pathway. This paper is trying to find a new target of anti-fibrosis therapy in SSc.Objective:To establish animal model of SSc and to investigate the effects of resveratrol (Res), the activator of SIRT1, on fibrosis of lung and skin.Methods:First, we established SSc animal model by daily subcutaneous injection of bleomycin (BLM) for4weeks in Balb/c mice. Then we fed the mice with Res. We observed the change in skin and lung with expression of the deacetylase SIRT1. The pathology was shown by hematoxylin-eosin (HE) staining. The expression of α-smooth muscle actin (a-SMA) was measured by immunohistochemistry. Collagen content was measured by hydroxyproline analysis. The expression of SIRT1, a-SMA and pro-collagen Ⅲ mRNA were assessed by RealTime PCR.Results:Daily subcutaneous injection of BLM for4weeks in Balb/c mice could successfully establish a mouse model of SSc. The thickening of skin and the inflitration of inflammatory cells and fibrosis of lung could be observed. The number of a-SMA positive cell and the expression of pro-collagen Ⅲ mRNA were increased (P<0.05). Meanwhile, the expression of SIRT1mRNA was decreased (P<0.05). The pathological changes in skin and lung could last for more than3weeks after the4weeks injection of BLM. Treated with Res, the pathological changes were alleviated and the number of a-SMA positive cell in lung and skin was decreased (P<0.05in some group). But there was no significant derease of the expression of SIRT1mRNA in lung.Conclusion:Daily subcutaneous injection of BLM for4weeks could successfully establish a mouse model of SSc with observed lung diseases and the decreased expression of SIRT1mRNA in lung. Res could inhibit the pathological changes of SSc mouse model in skin and lung.