小鼠暴发型病毒性肝炎肝组织基因表达谱的分析  

Microarray Analysis of Gene Expression in Liver Tissue from Balb/cJ Mice with MHV-3-induced Fulminant Hepatitis

作　　者：王洪武[1] 周耀勇[1] 邹勇[1] 严伟明[1] 罗小平[2] 宁琴[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院感染科/感染免疫研究室,武汉430030 [2]华中科技大学同济医学院附属同济医院儿科,武汉430030

出　　处：《华中科技大学学报（医学版）》2009年第1期6-10,共5页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家重点基础研究发展计划("973"计划)(No.2005CB522901;No.2007CB512900);国家自然科学基金(No.30571643;No.30672380)资助项目

摘　　要：目的分析小鼠暴发型病毒性肝炎肝组织基因表达谱,初步确定参与暴发型病毒性肝炎发病分子机制的相关基因。方法100 PFU3型鼠肝炎病毒(MHV-3)感染Balb/cJ小鼠,建立了暴发型病毒性肝炎模型,同等量病毒感染A/J小鼠后24 h取肝组织作为对比分析标本。应用含有16 463条Oligo DNA的小鼠基因表达芯片,检测两组小鼠间的基因差异表达谱。荧光定量逆转录聚合酶链反应法检测目标基因H2-EA的表达变化,验证芯片分析的初步结果。结果MHV-3感染Balb/cJ小鼠和A/J小鼠后其肝组织差异表达基因共140条,包括细胞代谢、细胞信号、细胞运输、转录调控以及免疫相关类等基因。其中2倍以上差异表达基因中与免疫功能密切相关的基因22条。结论暴发型肝炎过程中宿主基因表达谱发生了变化,共同参与了免疫致病机制,其中主要为细胞代谢和免疫相关类基因。Objective To analyze the differences of gene expression in liver tissue from mice with MHV-3-induced fulminant hepatitis with cDNA microarray and to investigate genes involved in disease development. Methods Animal models of fulminant viral hepatitis were established in susceptible strain Balb/cJ mice after 100 PFU of MHV-3 infection. MHV-3 resistant strain A/J mice undergoing the same treatment were set up as controls. Microarray consisting of 16 463 murine Oligo cDNA and labeled cDNA from liver tissue in both 10 Balb/cJ mice and 10 A/J mice were applied to analyze the differentially expressed genes. Relative ratios of gene expression individuals were obtained by comparing the hybridization results, by ScanArray Express scanning and by GenePixPro 4.0 software analysis, of cy5-1abelled cDNA from A/J mice with those of cy3-1abelled cDNA from Balb/cJ mice. Then H2-EA and GAPDH gene expression profile in comparative samples from both MHV-3 infected Balb/ cJ and A/J mice were confirmed by real-time fluorescent quantitative PCR. Results From the scanning results, it was found that 140 （0.9%） genes were differentially expressed, with 62 genes being up regulated and 78 genes being down-regulated, respectively. Besides 33 unknown genes were differentially expressed, most of them were involved in cell metabolism, ceil signaling, cell transport, cell transcription regulation and immune function. Conclusion The findings suggest that a series of host factor and host gene expression are changed and involved in disease development of MHV-3-induced routine fulminant hepatitis. Most of differentially expressed genes belong to the groups that are important in cell metabolism and immune function. Discovering such candidate genes may be help to study the pathogenesis of fulminant hepatitis.

关 键 词：微矩阵基因芯片 免疫 基因表达 暴发型肝炎 

分 类 号：R392.1[医药卫生—免疫学]