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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 study the molecular mechanism of toxic effects of rifampicin, an anti-tuberculosis drug, on rat liver using gene chip technology. Methods: Twenty Wistar rats were randomly divided into control group and rifampicin group, with 10 rats in each group. Rifampicin (100 mg.kg-1) and an equal volume of normal saline were administered orally for 14 consecutive days. The effect of rifampicin on rat liver gene expression profile was studied by cDNA microarray. The toxic mechanism of rifampin on rat liver was explored based on the biological function of differentially expressed genes. Results: There were 19 different expression genes in the rifampin group and the control group, including 11 up-regulated genes, down-regulated genes and 18 known genes, including 18 genes that are related to liver enzyme activity, oxidative stress and specificity Immune and other related genes. Conclusion: Rifampicin can cause significant changes in gene expression profile in rat liver. This study is very important for clarifying the mechanism of liver injury of rifampicin.