中文摘要：

目的 通过蛋白质组学的研究技术手段,筛选Ac-SDKP抗矽肺纤维化疗效和矽肺肺组织中与病变相关的特异蛋白质.方法 非暴露式支气管一次性灌注二氧化硅（SiO2）构建大鼠矽肺模型（4、8周）,并予以Ac-SDKP抗纤维化治疗和预防治疗,对照组（4、8周）支气管灌注等量氯化钠溶液.提取肺组织蛋白样品经双向电泳分离,胶体考马斯亮蓝染色显示蛋白点.扫描输入计算机,用ImageMaster 6.0图像分析软件对凝胶进行分析,差异蛋白判定标准为该蛋白点在两组间（对照组4、8周组分别与矽肺4、8周组比较,Ac-SDKP抗纤维化治疗组与矽肺8周组比较,Ac-SDKP预防治疗组与矽肺8周组比较）差异有统计学意义（P＜0.05）,且volume％值上下变化超过30％.将凝胶中的差异蛋白点切出,经胶内胰蛋白酶解,并行基质辅助激光解吸电离飞行时间质谱（MALDI-TOF-MS）获得肽质量指纹谱并对蛋白质进行分析.结果 共筛选到33个差异蛋白,其中与对照4周组比较,矽肺4周组有17个差异蛋白表达上调,11个差异蛋白表达下调;与对照8周组比较,矽肺8周组有16个差异蛋白表达上调,12差异个蛋白表达下调;与矽肺8周组比较,Ac-SDKP抗纤维化治疗组有5个蛋白表达上调,6个差异蛋白表达下调;与矽肺8周组比较,Ac-SDKP预防治疗组有8个差异蛋白表达上调,10个差异蛋白表达下调.结论 筛选到与矽肺纤维化形成和Ac-SDKP抗矽肺纤维化作用相关的差异蛋白,多涉及调控细胞增殖、凋亡、炎症反应和上皮-间质转化,以及信号转导通路等多方面的功能.

英文摘要：

Objective To perform a comparative proteomic analysis for identification of pulmonary proteins related to the progression of silicosis and anti-fibrotic effect of N-acetyl-seryl-aspartyl-lysyl-proline （Ac-SDKP）.Methods Bronchial instillation of SiO2 powder （for 4 or 8 weeks） was applied in rats to establish a silicosis model.Ac-SDKP treatment was performed before （prevention group） or after （treatment group） SiO2 instillation.The control group was treated by bronchial instillation of sodium chloride solution of the same volume as SiO2 powder for 4 or 8 weeks.Proteins in lung tissue were separated by two-dimensional gel electrophoresis and stained with colloidal Coomassie brilliant blue.The gel images were scanned with the Lab Scan Ⅲ system and analyzed with Imagemaster 6.0.The protein spots with significant differences between two groups （i.e.,P value was less than 0.05 in One-way ANOVA） and with a change in volume over 30% were defined as differential proteins.Comparison was performed between the silicosis group and control group after 4 or 8 weeks,between the Ac-SDKP treatment group and silicosis group after 8 weeks,and between the Ac-SDKP prevention group and silicosis group after 8 weeks.The differentially expressed proteins were subjected to in-gel digestion with trypsin and MALDI-TOF-MS and Mascot search engine analysis to identify these proteins.Results Thirty-three differential proteins were identified.In comparison with the control group （4 weeks）,the silicosis group （4 weeks） had 17 up-regulated proteins and 11 down-regulated proteins.In comparison with the control group （8 weeks）,the silicosis group （8 weeks） had 16 up-regulated proteins and 12 down-regulated proteins.In comparison with the silicosis group （8 weeks）,the Ac-SDKP treatment group had 5 up-regulated proteins and 6 down-regulated proteins,and the Ac-SDKP prevention group had 8 up-regulated proteins and 10 down-regulated proteins.Conclusion Critical regulatory proteins related to silicotic fibrosis a