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1、河南科技大學(xué)學(xué)報(醫(yī)學(xué)版)2014年3月第32卷第1期基礎(chǔ)醫(yī)學(xué)·對乙酰氨基酚誘導(dǎo)小鼠藥物性肝損傷中PCNA的表達趙瓊,符曉楠,李三強摘要:目的研究對乙酰氨基酚(Acetaminophen,AAP)誘導(dǎo)的小鼠藥物性肝損傷過程中增殖細胞核抗原(PCNA)表達的動態(tài)變化,進一步闡明PCNA在藥物性肝損傷中的重要作用。方法利用AAP溶液(550mg/kg)腹腔注射誘導(dǎo)小鼠藥物性肝損傷。取正常對照小鼠和注射AAP后6、24、48、72h的小鼠肝臟制備勻漿液,利用蛋白印跡的方法檢測小鼠肝損傷過程中PCNA的表達變化;同時檢測各時間點小鼠血清中AST和ALT酶活變化。結(jié)果小鼠注射
2、對乙酰氨基酚后,血清中AST和ALT酶活逐漸升高,24h達到高峰后逐漸降低,72h恢復(fù)到接近正常水平。PCNA在注射對乙酰氨基酚后6h,其表達量顯著下降,在24h表達量達到最低值,隨著損傷后的修復(fù),PCNA的表達量逐漸增高,72h逐漸恢復(fù)接近正常水平。結(jié)論PCNA在AAP誘導(dǎo)的小鼠藥物性肝損傷過程中表達出現(xiàn)顯著變化,AAP誘導(dǎo)的藥物性肝損傷過程存在一個損傷與修復(fù)逐漸變化的過程。關(guān)鍵詞:PCNA;對乙酰氨基酚;藥物性肝損傷中圖分類號:R634文獻標(biāo)志碼:A文章編號:1672—688X(2014)01—000I一02ExpressionAnalysisofPCNADur
3、ingDrug-inducedLiverInjuryInducedbyAcetaminopheninMiceZHAOQiong,F(xiàn)UXiao·nan,LISan—qiang(FirstAfiliatedHospital,HenanUniversityofScienceandTechnology,Luoyang471003,China)Abstract:ObjectiveTostudythedynamicchangesofPCNAduringdrug—inducedliverinjuryinducedbyacetaminopheninmiceandfurthercla
4、rifytheimportantrolesofPCNAinthedrug-inducedliverinjury.Methods24healthymalemicewereinjectedintraperitoneaⅡyacetaminophensolution(dilutedwithsaline,550mg/kg).Eyebloodwasrespectivelycollectedat6,24,48,72hafteracetaminopheninjection.Serumwasseparated,andthenASTandALTactivityweremeasured.
5、Atthesametime,theliversofmicewerepreparedfor10%liverhomogenate.Sixmicewereusedateachtimepoint.Atthesametime,sixnormalmicewereusedascontrols.WesternblottingwasusedtodetecttheexpressionchangesofPCNAduringacuteliverinjuryinmice.ResultsASTandALTactivityweregraduallyincreasedwithtimedelayed
6、andgottothepeaklevelsat24h,thengraduallyrecoveredtothenormallevelat72hafteracetaminopheninjection.TheexpressionofPCNAwassignificantlydecreasedat6handgottothelowestlevelat24h.ThentheamountofPCNAexpressiongraduallyreturnedtonormallevelat72hafterAAPinjection.ConclusionTheexpressionofPCNAi
7、ssignificantlychangedduringdrug—inducedliverinjuryinducedbyacetaminopheninmice,whichindicatesthattheprocessofacuteliverinducedbyAAPincludesgradualprocessofinjuryandrepair.Keywords:PCNA;acetaminophen;acuteliverinjury乙酰氨基酚(AAP)在大劑量使用時,可引起人和動物嚴重的藥物性肝臟損傷,學(xué)界已有一些對其基金項目:河南省高校科技創(chuàng)新人才支持計劃資助項目(