酒精对丙型肝炎病毒复制的影响及机制研究.pdf

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1、生堡微生塑堂麴免疫堂塞志20生年5月第34卷第5期ChinJMicmbiolImmunol。May2014，Vo1．34．N0．5·397·．病毒学．酒精对丙型肝炎病毒复制的影响及机制研究陈晖苏锦明李或陈荣凤刘洁王敏连赵芳凝王洪曾锦荣【摘要】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HCVRNA；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HCVCore、IFN-0l、IFN-B、

2、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10mmol／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40mmol／L酒精处理肝细胞，可使细胞IFN．Ct、IFN．B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·OL和IFN—B)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

3、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．疗效降低的原因之一。【关键词】丙型肝炎病毒；酒精；I型干扰素；固有免疫EfectsofalcoholonHCVreplicationanditsmechanismChenHui，SuJinming，LiYu，ChenRong-，厶u加，WangMinlian，ZhaoFangning，WangHong，zeJinrong．GeriatricsDigestionDepart-mentofInternalMedicine，theFirstAffiliatedHo

4、spitalofGuangxiMedicalUniversity，Nanning530021，ChinaCorrespondingauthor：ChenHui，Email：chenhui680804@163．com【Abstract】ObjectiveToinvestigatetheefectsofalcoholonhepatitisCvires(HCV)replicationandtypeIinterferonsignalingpathwayinhumanhepatocytes．MethodsPrimaryhepatocyteswere

5、treatedwitlldiferentconcentrationsofalcoho1．andtheninfected’vitllHCV．TheinfectedcellswerecollectedtomeasurethelevelofHCVRNA．Thealcohol—treatedhepatocyteswerealsocolectedtodetecttheexpressionofHCVCore，IFN—，IFN-B，IRF-7，suppressorofcytokinesignalingSOCS-2andSOCS-3atmRNAandpr

6、oteinlevelsbyreal-timequantitativePCRandELISAorWesternblot，respectively．ResultsAlcoholtreatmentenhancedHCVinfectionandreplicationinprimaryhepatocytesatconcentrationshigherthan10mmol／Linadose—dependentmanner(P

7、ssionofIFN-0【，IFN—BandIRF-7atmRNAandproteinlevels，andincreasedtheexpressionofSOCS-2andSOCS-3atmRNAandproteinlevels．ConclusionAlcoholtreatmentcoulddamagethehostin-nateimmunityinhumanhepatocytesandpromoteHCVreplicationbyreducingtheexpressionoftypeIinter-feron(IFN-andIFN-8)a

8、ndIRF-7andincreasingtheexpressionofnegativeregulatorsincludingSOCS-2andSOCS-3．Theseresultsdemons