外源质粒DNA对小鼠肝脏基因表达谱的影响

Effect of Foreign Plasmid DNA on Gene Expression Profile of Liver in Mice

研究了外源质粒DNA经胃肠道吸收可能对肝脏产生的作用机制。给Balb/c小鼠灌胃质粒pcDNA3 200μg,在灌胃后4 h分离肝脏,提取肝脏的总RNA。利用寡核苷酸芯片对灌胃质粒pcDNA3后的Balb/c小鼠肝脏进行基因表达谱研究。结果发现17 664个基因中,表达上调100条,表达下调41条。按基因功能分类,表达上调的基因可分为免疫应答基因、转录因子基因、信号转导基因、转运相关基因及代谢相关基因等;表达下调的基因主要为脂质代谢基因。灌胃外源质粒DNA后,肝脏组织主要表现为急性时相反应的加强、免疫反应的活化、细胞信号通路的活化以及脂质代谢途径的抑制。表明外源质粒DNA通过胃肠道途径可广泛调控肝脏的基因表达。

To have more insight into the possible mechanism of effect of foreign plasmid on liver in mice, mice were oral administered with 200μg of plasmid pcDNA3 and liver were isolated at 4 h after oral administration. Total RNA was extracted from liver and liver gene expression profile of Balb/c mice was analyzed by using oligonucleotide array after oral administration of plasmid pcDNA3. The result showed 100 genes were up-regulated and 41 were down-regulated among the total 17664 genes. The up-regulated genes could be functionally categorized into immune response, transcription factors, signal, transport and metabolic genes; and the down-regulated genes were mainly lipid metabolism genes. The biological processes are mainly involved in the acute phase response, the activation of immune response, cellular signal pathway, and the suppression of lipid metabolism in liver after oral administration of plasmid DNA. Foreign plasmid DNA may widely modulated gene expression in the liver after oral administration, this brings new clues for studying the mechanism of absorption and effect of foreign plasmid DNA in the liver.