用cDNA微阵列技术研究HBV X基因与AFB_1对HBVx转基因小鼠药物代谢酶基因表达谱的影响

The effect of aflatoxin B_1 and HBV X gene on expression profiles of drug-meta bolizing enzymes genes in transgenic mice with HBVx gene by cDNA microarray

目的 研究乙型肝炎病毒X基因和黄曲霉毒素诱发小鼠肝癌过程中药物代谢酶基因表达谱的变化,探讨两因素协同致肝癌的机制。方法 用BiostarM 40s微阵列芯片比较研究HBVx组、AFB1 组和(AFB1+HBVx)组的肝组织基因表达谱与对照组的差异。结果 各实验组分别与对照组相比基因表达谱发生了明显的改变,各实验组上调与下调的基因数目分别为(AFB1+HBVx)组69项;AFB1 组101项;HBVx组35 项;其中与代谢酶相关的基因有18 项表达发生改变,分别为(AFB1 +HBVx)组13项(13/18,72%);HBVx组4项(4/18,22%);AFB1 组8项(8/18,44%)。结论 小鼠受到HBV X基因和AFB1双重攻击后,其体内的GST、EPHX和UDPGT等药物代谢酶基因表达水平明显低于HBVx组和AFB1 组。HBV与AFB1 协同致癌的分子机制很可能与两者引起药物代谢酶基因表达水平下调有关。

Objective To investigate difference of gene expression profiles for drug-metabolizing enzymes by AFB 1 treatment and HBV X gene expression inducing hepatocarcinogenesis in transgenic mice with HBVx gen e and to explore the molecular mechanism of the synergetic hepatocarcinogenesis effect of both HBV and AFB 1 in the development of HCC.Methods Using BiostarM-40s cDNA microarray to analyze the diff erent expression of liver tissues between the blank group and the experimental g roups including HBVx group, AFB 1 group and the combine group of HBVx and AFB 1.Results Evident difference was observed in experimental groups when compared with the blank group. The number of aberrant expressions including up-regulated and down-regulated genes in HBVx group, AFB 1 group and the com bine group were 35,101 and 69,respectively. We also found 18 aberrant expression which involved in metabolizing enzymes, among 18 genes, 4 out of 18 (22%) in HB Vx group, 8 out of 18 (44%) in AFB 1 group and 13 out of 18 (72%) in the combin e group.Conclusion The gene expression levels of those genes encoding d rug-metabolizing enzymes including GST,EPHX and UDPGT are significantly lower in mice, which suffered from dual attack of HBV X gene plus AFB 1 than in those which suffered from single attack of HBV X gene or AFB 1.The mechanisms of HBV and AFB 1-induce synergetic hepatocarcinogenesis may be correlation with the expression levels down-regulated of drug-metabolizing enzymes genes.