抗结核病药物利福平致大鼠肝脏损伤的基因表达谱分析  

Gene expression profiles of rifampicin-injured rat liver using cDNA micoarray

作　　者：廖艳[1] 彭双清[2] 张立实[3] 

机构地区：[1]北京中医药大学基础医学院养生康复系,北京100029 [2]中国人民解放军疾病预防控制所毒理学评价研究中心,北京100071 [3]四川大学华西公共卫生学院营养与食品卫生学教研室,成都610041

出　　处：《中国新药杂志》2011年第13期1212-1216,共5页Chinese Journal of New Drugs

基　　金：国家“重大新药创制”科技重大专项(2009ZX09501-034);国家自然科学基金(30371705);国家科技支撑计划课题项目(2006BAK02A02)

摘　　要：目的:利用基因芯片技术研究抗结核病药物利福平对大鼠肝脏毒性效应的分子机制。方法:20只Wistar大鼠随机分为对照组和利福平组,每组10只,分别灌胃给予利福平(100 mg.kg-1)和等体积生理盐水,连续14 d。以cDNA微阵列技术研究利福平对大鼠肝脏基因表达谱的影响,根据差异表达基因的生物学功能探讨利福平对大鼠肝脏的毒性机制。结果:利福平组与对照组杂交的表达差异基因共19个,其中上调基因11个,下调基因8个,功能已知基因18条,主要包括一些与肝药酶活性、氧化应激和特异性免疫等相关的基因。结论:利福平可导致大鼠肝脏基因表达谱明显变化。该研究对阐明利福平的肝损伤机制具有十分重要的作用。Objective：To investigate the gene expression profiles of rat liver tissue injured by rifampicin（RFP） using cDNA microarrays.Methods：Wistar rats were divided into 2 groups（10 in each group）,and administrated（ig） with 100mg·kg-1 RFP or equal-volume saline for 14d,respectively.The gene expression profiles were detected by cDNA microarrays.The differentially expressed genes significantly correlated with liver injury were screened and analyzed.The mechanisms of liver injury caused by RFP were specifically analyzed at level of gene expression based on the biological functions of those differentially expressed genes.Results：Totally 19 differentially expressed genes were found in the rats administrated RFP.Among them,11 genes were up-regulated,while the other 8 genes were down-regulated.These differentially expressed genes were functionally related to the changes in CYP450-related genes,and the genes relevant to oxidation stress and special immune.Conclusion：RFP can cause remarkable changes in the gene expression profiles in rat liver cells,which is important for further elucidating the mechanisms of this type of liver injury.

关 键 词：利福平 基因表达谱 肝毒性 大鼠 

分 类 号：R965[医药卫生—药理学]