中文摘要：

目的 探讨白藜芦醇对SSc动物模型肺及皮肤病变的作用,旨在寻找SSc抗纤维化治疗新的靶点.方法 采用博来霉素诱导BALB/c小鼠SSc模型,观察其肺部及皮肤病变情况及SIRT1的表达情况.然后,应用白藜芦醇饲喂进行干预,观察病变改善情况及SIRT1的表达.观察的主要指标有：肺组织及注射处皮肤苏木精-伊红（HE）染色观察皮肤及肺组织病理改变;应用免疫组织化学法检测注射处皮肤及肺组织中α-平滑肌肌动蛋白（α-SMA）含量;应用荧光定量PCR （Real Time-PCR）法检测肺组织中SIRT1、Ⅲ型前胶原的mRNA表达.组间比较采用单因素方差分析,两两比较采用LSD-t检验.结果 博来霉素连续皮下注射4周后,小鼠HE染色可见皮肤增厚,肺泡间隔增厚、炎性浸润和部分区域纤维化表现,肺及皮肤α-SMA阳性细胞较对照组显著增多[皮肤：（26.4±5.9）个/视野和（4.4±2.2）个/视野,肺：（14.6±4.6）个/视野和（2.4±1.1）个/视野,P＜0.01）,肺部Ⅲ型前胶原表达上升（相对GAPDH表达量：1.06±0.24和0.45±0.14,P＜0.05）、SIRT1表达下降（相对GAPDH表达量：1.01±0.51和5.03±1.59,P＜0.05].应用Res干预后,皮肤及肺部病理改变有所减轻,皮肤及肺部α-SMA阳性细胞减少[皮肤：模型组（26.4±5.9）个/视野和高剂量组（10.0±3.5）个/视野,模型组（26.4±5.9）个/视野和中剂量组（13.4±4.4）个/视野,肺：模型组（14.6±4.6）个/视野和高剂量组（8.8±3.5）个/视野,P＜0.05],肺组织中SIRT1及Ⅲ型前胶原表达较模型组差异无统计学意义.结论 博来霉素连续皮下注射可成功诱导SSc小鼠模型;Res干预可作为SSc治疗的新的方向.

英文摘要：

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 establish ed 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 one-way 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 expression 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