酒精對丙型肝炎病毒復(fù)制的影響及機制研究.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·．病毒學(xué)．酒精對丙型肝炎病毒復(fù)制的影響及機制研究陳暉蘇錦明李或陳榮鳳劉潔王敏連趙芳凝王洪曾錦榮【摘要】目的探討酒精對丙型肝炎病毒(HCV)復(fù)制以及肝細(xì)胞I型干擾素及其信號通路因子的影響。方法將原代肝細(xì)胞用不同濃度的酒精進(jìn)行處理，再用HCV感染細(xì)胞，并在感染后收集細(xì)胞測定HCVRNA；用酒精處理原代細(xì)胞后用實時熒光定量PCR、ELISA和蛋白免疫印跡法測定細(xì)胞內(nèi)HCVCore、IFN-0l、IFN-B、

2、干擾素調(diào)節(jié)因子7(IRF-7)、細(xì)胞因子信號抑制物(SOCS)-2和SOCS-3的mRNA和蛋白表達(dá)。結(jié)果當(dāng)酒精濃度高于10mmol／L時，可增強HCV在原代肝細(xì)胞的感染和復(fù)制(P<0．05)，且呈現(xiàn)劑量依賴性；用40mmol／L酒精處理肝細(xì)胞，可使細(xì)胞IFN．Ct、IFN．B和IRF-7的mRNA和蛋白表達(dá)顯著降低，而顯著增加SOCS-2和SOCS-3的mRNA和蛋白表達(dá)。結(jié)論酒精可下調(diào)肝細(xì)胞I型干擾素(IFN·OL和IFN—B)和IRF-7的表達(dá)，上調(diào)負(fù)向調(diào)節(jié)因子SOCS-2和SOCS-3的表達(dá)，對宿主細(xì)胞天然抗病毒免疫造成損害，促進(jìn)

3、HCV復(fù)制，表明酒精濫用者肝細(xì)胞的固有免疫受損可能是HCV慢性感染增強以及IFN．療效降低的原因之一?！娟P(guān)鍵詞】丙型肝炎病毒；酒精；I型干擾素；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．a(chǎn)ndtheninfected’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