异烟肼利福平两药联用致大鼠肝脏损伤的基因表达谱分析

Gene expression profile in injured rat liver induced by isoniazid and rifampicin using cDNA microarray

目的:利用基因芯片技术研究抗结核病药物异烟肼和利福平两药联用对大鼠肝脏毒性效应的分子机制。方法:将20只Wistar大鼠随机分为两组,每组10只,分别为两药联用组与对照组,前者灌胃给予异烟肼(400 mg·kg-1)和利福平(100 mg·kg-1),后者灌胃给予等体积0.9%Na Cl溶液,连续14 d。以c DNA微阵列技术研究异烟肼和利福平两药联用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异烟肼和利福平两药联用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55条,其中上调基因36条,下调基因19条,功能已知基因25条,已知功能基因主要包括一些与肝药酶活性、三大物质代谢、肝脏功能和抗氧化作用等相关的基因。结论:异烟肼和利福平两药联用可导致大鼠肝脏基因表达谱明显变化,这对阐明异烟肼和利福平两药联用的肝损伤机制具有十分重要的意义。

Objective： To investigate the changes of the gene expression profile of rat liver tissue injured by co-administration of isoniazid （INH） and rifampicin （RFP） using cDNA microarrays. Methods- Twenty Wistar rats were divided into 2 groups （10 in each group）, and administrated （ig） with the combination of INH （400 mg·kg^-1 ） and RFP （ 100 mg·kg^-1 ） or equal-volume saline, respectively, for 14 days. 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 co-administration of INH and RFP were specifically analyzed at level of gene expression based on the biological functions of those differentially expressed genes. Results： Totally 55 differentially expressed genes were found in the rats with the combination of INH and RFP. Among them, 36 genes were up-regulated, while the other 19 genes were down-regulated. These differentially expressed genes were functionally related to the changes in metabolism of three substances （glucose, protein, and lipid） CYP450-related genes, and the genes relevant to the , liver function and antioxidatiou. Conclusion： The combination of INH and RFP causes the remarkable changes of the gene expression profiles in rat liver, which is important for further elucidating the mechanisms of liver injury caused by co-administration of INH and RFP.