60Co-γ照射后早期小鼠肝组织基因表达谱
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上海市自然科学基金(04ZR14083).


Hepatic gene expression profile early after 60Co-γ irradiation in mice
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    摘要:

    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(4096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、Nqol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.

    Abstract:

    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

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