应用基因芯片技术研究原发性胆汁性肝硬化患者外周血单个核细胞基因表达谱特征  

Gene expression profiles of peripheral blood mononuclear cells in primary biliary cirrhosis patients

作　　者：张磊[1] 李永哲[1] 马丹旭[1] 李晞[1] 张奉春[1] 

机构地区：[1]中国医学科学院北京协和医学院北京协和医院风湿免疫科, 100032

出　　处：《中华风湿病学杂志》2011年第12期829-833,I0001,共6页Chinese Journal of Rheumatology

基　　金：国家自然科学基金（30471617、30640084、30872331、81072486）;国家“十一五”科技支撑计划（2008BA159802、2008BAI一59803）

摘　　要：目的应用基因芯片技术分析原发性胆汁性肝硬化患者外周血单个核细胞的基因表达谱特征。方法选取9例原发性胆汁性肝硬化患者、9名健康对照为研究对象，提取其外周血单个核细胞总RNA，进行人类全基因组寡核苷酸芯庶〈约22000个基因）检测，筛选出差异表达基因及相关信号通路。结果原发性胆汁性肝硬化患者外周血单个核细胞中差异表达的基因共有79个，其中21个表达上调，58个表达下调。这些基因对应着27条信号通路，其中有6条通路参与了免疫调控及细胞凋亡过程，分别是自然杀伤细胞介导的细胞毒通路、Toll样受体信号通路、抗原加工提呈通路、细胞因子相互作用通路、T细胞受体信号通路、细胞凋亡通路。结论原发性胆汁性肝硬化患者外周血单个核细胞中存在特有的差异表达基因，针对这些基因及相关信号通路的进一步研究，将为探索发病机制和寻找生物标志物提供新的方向。Objective To explore the differentially expressed genes in peripheral blood mononuclear cells of patients with primary biliary cirrhosis and compare it with healthy controls. Methods Peripheral blood mononuclear cells were isolated from 9 primary biliary cirrhosis patients and 9 age and sex matched healthy controls. Total RNA was extracted from peripheral blood mononuclear cells and analyzed by human genome oligonucle0tide microarrays （22K）. The differences of gene expression and signaling pathway of patients and healthy controls were compared. Results Seventy-nine genes differentially expressed in primary biliary cirrhosis were identified by microarray analysis,in which 21 were up-regulated and 58 were downregulated. The genes were further categorized into 27 signaling pathways, in which 6 pathways were involved in immune regulation and apoptosis： natural killer cell mediated cytotoxicity pathway, toll-like receptor signaling pathway, antigen processing and presentation pathway, cytokine-cytokine receptor interaction pathway, T cell i：eceptor signaling pathway and apoptosis pathway. Conclusion This study has identified that some genes are different in transcription expression in the primary biliary cirrhosis patients. It may provide new clues for the pathogenesis and biomarker studies.

关 键 词：肝硬化 胆汁性 寡核苷酸序列分析 基因表达谱 

分 类 号：R575.2[医药卫生—消化系统]