吸烟对肺组织D4-GDI表达的影响及其与慢性阻塞性肺疾病相关性的蛋白质组学研究  

Proteomics Research Focus on The Affection of Smoking to D4-GDI Expression in Lung Tissue and The Relationship With Chronic Obstructive Pulmonary Disease

作　　者：欧阳卿[1,2] 胡瑞成 戴爱国 谭双香 肖志强[3] 汤参娥[3] 

机构地区：[1]湖南省老年医院-湖南省老年医学研究所呼吸疾病研究室,长沙410016 [2]南华大学研究生院,衡阳421001 [3]中南大学湘雅医院卫生部肿瘤蛋白质组学重点实验室,长沙410008

出　　处：《生物化学与生物物理进展》2010年第11期1204-1211,共8页Progress In Biochemistry and Biophysics

基　　金：湖南省自然科学基金(06JJ4056);湖南省科技厅科研基金(2007FJ3016;2008FJ4206;2009JT3054);湖南省卫生厅科研基金(B2003-130;B2008-026)资助项目~~

摘　　要：慢性阻塞性肺疾病(COPD)是环境因素与遗传因素共同作用的结果,而吸烟是导致COPD发生的最主要危险因素,然而,吸烟导致COPD的机制及COPD的遗传易感机制目前尚未完全阐明.蛋白质组学研究方法具有高效和信息含量丰富的特点,为COPD研究提供了有力的帮助,被认为在COPD的研究领域具有广阔的前景.运用二维凝胶电泳和基质辅助激光解吸电离飞行时间质谱蛋白质组学研究方法结合生物信息学技术,对不吸烟者、非COPD吸烟者和吸烟COPD患者的肺组织进行蛋白质组比较,共鉴定出24种表达差异蛋白.研究发现,非COPD吸烟者肺组织ρ-GDP解离抑制因子2(D4-GDI)表达水平为不吸烟者的1.7倍,吸烟COPD患者肺组织D4-GDI表达水平接近非COPD吸烟者的2倍.通过免疫组织化学染色和Western-blotting检测对肺组织D4-GDI表达水平进行验证,获得了与蛋白质组学研究相一致的结果.结果首次说明:吸烟能够导致肺组织D4-GDI表达水平升高,D4-GDI参与了COPD的发病机制而且可能与COPD易感性相关.Chronic obstructive pulmonary disease（COPD） development is the result of environmental factors interact with hereditary factors,and smoking is the primary cause for COPD development.Nevertheless,both the mechanisms of smoking leads to COPD and the mechanisms of COPD hereditary susceptibility are not well clarified so far.Proteomics research features high efficiency and rich information,which had provided strong help for COPD study,and considered has broad prospects in COPD research area.Two dimensional gel electrophoresis and matrix assisted laser desorption/ionization time of flight mass spectrometry were used in proteomics research to compare the lung tissue proteome of never-smokers,non-COPD smokers and COPD smokers.By combined with bioinformatics technology,24 proteins were identified to be differentially expressioned between groups.The D4-GDI expression level in lung tissue of non-COPD smokers was 1.7 times to never-smokers,while the D4-GDI expression level in lung tissue of COPD smokers was nearly twice to non-COPD smokers.For verification,D4-GDI expression level in lung tissue was detected by immunohistochemical staining and Western-blotting,and the results was consistent with proteomics research.The results of this study for the first time to description：Smoking can up-regulate D4-GDI expression level in lung tissue,D4-GDI involved in the pathogenesis of COPD and may be associated with COPD susceptibility.

关 键 词：慢性阻塞性肺疾病 蛋白质组学 二维凝胶电泳 质谱分析 ρ-GDP解离抑制因子2(D4-GDI) 

分 类 号：Q81[生物学—生物工程] R56[医药卫生—呼吸系统]