丙型肝炎病毒感染影响载脂蛋白B基因甲基化水平

Hepatitis C Virus Infection Influence the Methylation of Apolipoprotein B Gene

目的 探讨丙型肝炎病毒（HCV）感染与载脂蛋白B（ApoB）DNA甲基化的关系.方法 采用生化分析仪Olympus 5400检测HCV患者和健康对照者血清ApoB的水平,RT-PCR检测人肝癌细胞系Huh7和含JFH-1株HCV病毒感染的Huh7.5.1细胞系中ApoB mRNA的水平,比较两种细胞系DNA甲基化酶活性的差别,分析加入不同剂量的甲基化酶抑制剂后ApoB mRNA的水平变化.结果 HCV患者ApoB的水平为0.67±0.14 μmol/L,健康对照组为0.98±0.26 μmol/L,ApoB mRNA在Huh7.5.1细胞中的表达水平低于Huh7细胞,且HCV感染可以增加细胞核内DNA甲基化酶的活性,甲基化酶抑制剂能剂量依赖地促进ApoB mRNA表达.结论 HCV通过增加DNA甲基化酶活性来抑制ApoB的表达.

Objective To explore the relationship between hepatitis C virus infection （HCV） and apolipoprotein B （ApoB） DNA methylation. Methods Serum ApoB levels in patients with HCV infection and in healthy individuals were measured by biochemical analyzer Olympus 5400,ApoB mRNA levels in hepatocellular carcinoma cell line Huh7 and Huh7.5. 1 infected with HCV JFH-1 were measured by RT-PCR,and DNA methyltransferase activity differences between the two cell lines were also compared. After demethylating agent of different concentrations added to HuhT. 5.1 cells,changes of ApoB mRNA, were analysed. Results ApoB was significantly reduced in patients（0.67±0. 14μmol/L） as compared to healthy individuals （0.98±0.26 μmol/L）,expression levels of ApoB mRNA were lower in HuhT. 5.1 cells than in Huh7 cells,and DNA methyhransferase activity in the nuclear was increased,while ApoB mRNA levels were promoted in dose dependent manner with demethylating agent added. Conclusion HCV inhibits expression of ApoB by increasing the DNA methyltransferase activity.