CAJ | 학술논문

目的：探讨酒精对丙型肝炎病毒（HCV）复制以及肝细胞Ⅰ型干扰素及其信号通路因子的影响。方法将原代肝细胞用不同浓度的酒精进行处理，再用HCV感染细胞，并在感染后收集细胞测定HCV RNA；用酒精处理原代细胞后用实时荧光定量PCR、ELISA和蛋白免疫印迹法测定细胞内HCV Core、IFN-α、IFN-β、干扰素调节因子7（ IRF-7）、细胞因子信号抑制物（ SOCS ）-2和SOCS-3的mRNA和蛋白表达。结果当酒精浓度高于10 mmol／L时，可增强HCV在原代肝细胞的感染和复制（P＜0．05），且呈现剂量依赖性；用40 mmol／L酒精处理肝细胞，可使细胞IFN-α、IFN-β和IRF-7的mRNA和蛋白表达显著降低，而显著增加SOCS-2和SOCS-3的mRNA和蛋白表达。结论酒精可下调肝细胞Ⅰ型干扰素（ IFN-α和IFN-β）和IRF-7的表达，上调负向调节因子SOCS-2和SOCS-3的表达，对宿主细胞天然抗病毒免疫造成损害，促进HCV复制，表明酒精滥用者肝细胞的固有免疫受损可能是HCV慢性感染增强以及IFN-α疗效降低的原因之一。
목적：탐토주정대병형간염병독（HCV）복제이급간세포Ⅰ형간우소급기신호통로인자적영향。방법장원대간세포용불동농도적주정진행처리，재용HCV감염세포，병재감염후수집세포측정HCV RNA；용주정처리원대세포후용실시형광정량PCR、ELISA화단백면역인적법측정세포내HCV Core、IFN-α、IFN-β、간우소조절인자7（ IRF-7）、세포인자신호억제물（ SOCS ）-2화SOCS-3적mRNA화단백표체。결과당주정농도고우10 mmol／L시，가증강HCV재원대간세포적감염화복제（P＜0．05），차정현제량의뢰성；용40 mmol／L주정처리간세포，가사세포IFN-α、IFN-β화IRF-7적mRNA화단백표체현저강저，이현저증가SOCS-2화SOCS-3적mRNA화단백표체。결론주정가하조간세포Ⅰ형간우소（ IFN-α화IFN-β）화IRF-7적표체，상조부향조절인자SOCS-2화SOCS-3적표체，대숙주세포천연항병독면역조성손해，촉진HCV복제，표명주정람용자간세포적고유면역수손가능시HCV만성감염증강이급IFN-α료효강저적원인지일。
Objective To investigate the effects of alcohol on hepatitis C virus( HCV) replication and type I interferon signaling pathway in human hepatocytes .Methods Primary hepatocytes were treated with different concentrations of alcohol , and then infected with HCV .The infected cells were collected to measure the level of HCV RNA .The alcohol-treated hepatocytes were also collected to detect the expression of HCV Core, IFN-α, IFN-β, IRF-7, suppressor of cytokine signaling SOCS-2 and SOCS-3 at mRNA and protein levels by real-time quantitative PCR and ELISA or Western blot , respectively .Results Alcohol treatment enhanced HCV infection and replication in primary hepatocytes at concentrations higher than 10 mmol/L in a dose-dependent manner (P<0.05).Treatment with 40 mmol/L of alcohol significantly reduced the expression of IFN-α, IFN-βand IRF-7 at mRNA and protein levels , and increased the expression of SOCS-2 and SOCS-3 at mRNA and protein levels .Conclusion Alcohol treatment could damage the host in-nate immunity in human hepatocytes and promote HCV replication by reducing the expression of type Ⅰinter-feron ( IFN-αand IFN-β) and IRF-7 and increasing the expression of negative regulators including SOCS-2 and SOCS-3.These results demonstrated that the impairment of innate immunity in liver of alcohol abusers might contribute to the enhancement of HCV infection and result in poor therapeutic effect of IFN -α.