【摘要】 目的利用毒理基因芯片技术研究四环素肝脏毒性效应的分子机制。方法利用本室构建的小鼠毒理基因芯片和四环素致BALB/c小鼠肝毒性动物模型,观察不同剂量和时相点小鼠肝脏基因表达谱变化,利用Gene OntologyConsortium分析系统并结合层次聚类对差异表达基因进行初步功能分析。结果四环素作用后引发肝脏多种基因表达改变,聚类分析发现高、低剂量四环素作用的表达谱明显差异,高剂量各时相点差异基因聚类分为4类,涉及的分子机制包括能量代谢抑制,蛋白质合成和降解增加,抗氧化体系受损,信号转导基因表达改变促进凋亡发生,以及药物代谢相关酶系基因抑制等。结论毒理基因芯片技术能够为我们在分子水平上提供四环素对小鼠肝脏毒性损伤机制的众多线索,为进一步生物学效应研究奠定基础。更多还原

【Abstract】 Objective To study the molecular mechanism of the toxic effect for tetracycline acting on liver using toxicological microarray.Methods Utilizing the mouse toxicological microarray and animal model of tetracycline injuring BALB/c mouse liver,both of which were established by our department,we observed the gene expression profiles in different dose groups and at different time points after tetracycline treatment,and primarily analysed the function of these differentially expressed genes using Gene Ontology Consortium analysis system and hierarchical method.Results Multiple differentially expressed genes were found,and an obvious difference in the profiles was found in those treated with high-dose and low-dose tetracycline.The differentially expressed genes of all time points in high-dose group were divided to four clusters,which respectively related to the molecular mechanism of repressed enegy metabolism,enhanced protein synthesis and degradation,impared system of resisting oxidation,signal transduction genes changing to accelerate apoptosis,repressed genes associated of drug metabolism.Conclusion The analysis using toxicological microarray can offer us many clues on molecular level for studying the mechanism of the toxic effect of tetracycline acting on liver.更多还原