摘要
目的利用毒理基因芯片技术研究抗结核病药物异烟肼对大鼠肝脏毒性效应的分子机制。方法将20只Wistar大鼠随机分为对照组(n=10)和异烟肼组(n=10),分别用生理盐水和400mg/kg异烟肼连续灌胃14d,以cD-NA微阵列技术研究异烟肼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对大鼠肝脏的毒性机制。结果异烟肼组与对照组杂交的表达差异基因共37条,其中上调基因25条,下调基因12条,功能已知基因18条,已知功能基因主要包括一些与肝药酶活性、脂肪代谢和蛋白质代谢等相关的基因。结论异烟肼可导致大鼠肝脏基因表达谱明显变化,这对阐明异烟肼的肝损伤机制具有十分重要的作用。
Objective To investigate the changes of gene expression profile of rat liver tissue by cDNA microarrays. Methods Twenty Wistar rats in control group （ n = 10） and isoniazid （INH） group （ n = 10） were orally administrated with normal saline and 400 mg/kg INH for 14 days, respectively. The differentially expressed genes significantly correlated with liver injury were screened and analyzed. The mechanisms of liver injury caused by INH were specifically analyzed at level of gene expression based on the biological functions of those differentially expressed genes. Results Thirty-seven differentially expressed genes were found in the rats administrated with INH. Among them, 25 genes were up-regulated, while the other 12 genes were down-regulated. These differentially expressed genes were functionally related to the changes of CYP450-related genes, fatty acid metabolism, and protein metabolism. Conclusion INH can cause the remarkable changes of the gene expression profiles in rat liver cells, which is important for further elucidating the mechanisms of liver injury caused by INH
出处
《中国医学科学院学报》
CAS
CSCD
北大核心
2009年第3期308-314,I0001,I0002,共9页
Acta Academiae Medicinae Sinicae
基金
国家自然科学基金(30371705)
国家重大新药创制重大专项(2009)
军事医学科学院创新基金(2006A)~~
关键词
异烟肼
基因表达谱
肝毒性
大鼠
isoniazid
gene expression profile
hepatotoxicity
rat
