^(60)Co-γ照射后早期小鼠肝组织基因表达谱

Hepatic gene expression profile early after ^(60)Co-γ irradiation in mice

目的:以基因芯片技术研究辐射后小鼠肝脏的基因表达谱,从分子水平探讨辐射引起小鼠肝脏损伤的机制。方法:采用小鼠基因表达谱芯片(4 096个基因)对60Co-γ照射后48 h小鼠肝组织基因表达谱进行研究。RT-PCR验证基因芯片结果。结果:与正常小鼠相比,辐射后小鼠肝组织有124条基因差异表达,78条下调,46条上调。其中57条基因的功能已知,这些差异表达的基因按功能可分为6类:DNA修复和应激蛋白,细胞骨架,离子通道和转运蛋白,信号转导,免疫蛋白,代谢调控,其中下调基因主要为细胞骨架基因,而上调基因主要为细胞周期调控蛋白和转录因子。RT-PCR结果表明,Hspa5、Rasa3、Nqo1基因的表达和芯片结果一致。结论:辐射造成的肝损伤具有多靶点、多层次及多通路的特点。

Objective：To study the hepatic gene expression profile early after 60^Co-γ irradiation in mice with eDNA microarray, in an attempt to understand the molecular mechanism of irradiation damage to liver in mice. Methods： Total RNA was extracted from mice liver 2 days after irradiation with ^60Co-γ ray and from normal mice liver. Hepatic gene expression patterns of irradiated and normal mice were compared with eDNA microarray（4 096 genes）. RT-PCR was performed to validate the eDNA microarray results. Results： Compared with normal group, 124 genes showed a differential expression in irradiation group, with 46 genes upregulated（maily cell cycle and transcription regulation related proteins） and 78 down-regulated（mainly cytoskeletal genes）. Of the 124 genes, 57 had identified functions and could be divided into 6 groups： DNA repair and stress response,cytoskeleton, hydronium channel/transport protein, signaling transduction, intermediary metabolism, and immune related proteins. RT-PCR analysis indicated that the expression of heat shock 70kD protein 5 （HspaS）, RAS p21 protein activator 3 （Rasa3）,and NAD（P）H dehydrogenase, quinone 1 （Nqol） were consistent with eDNA microarray data. Conclusion： Irradiation-induced hepatic injury is of multi-target and multi-pathway.