实验性肝损伤动物模型的制备和评价

＊:1007-4287(2009)10-1477-03曲相如1,孙景春2,卢秀花1,胡婷婷1,曹姗姗1,曹　霞1＊(1.,130021;2.)　　,,、、,,,,。、、、,。1　1.1　(CCL4),、,、,,CCL4,CCL4,,。CCL4,。CCL4。DNA,,DNADNA,。CCL4,、、、、,[1]。1.2　D-(D-galactosamine,D-GalN)D-GalN100g/L,1MpH7.0,600-900mg/kg,24h,,24-48h,、[2]。D-GalN24h、、;SOD,MDA。D-GalNRNA,Ca2+,、D-GalN[3,4]。1.3　(acetaminophen,paracetamol,AP),,300-500mg/kg,2.5%,,24h,、[5,6]。AP,P450N-(NAPQI),NAPQI-S-GSH。,AP,,AP,AP,GSH,NAPQI,NAPQI,、,,。1.4　α-(A-Naphthylisothiocyanate,ANIT)ANIT,0.5%ANIT50mg/kg,。50mg/kg2/,12,,、[3]。ANIT,,,,,,,,ANIT[7]。1.5　,,。,0.35mmol/kg,4h0.28mmol/kg,2。,,,,P450,,;。,,,。1.6　(Dimethylnitrosamine,DMN)DMN,,。DMN15ul/kg,,,,—1477—　200910　13　10。1.5%DMN1ml/kg,3/4、、、、[8]。DMN,,DMN6hDNA,24h,DMN,[9]。1.7　(Thioa-cetamide,TAA)TAA。4%TAA0.2g/kg·d,3/,10,,β1mRNA,、、、[10]。2　2.1　(BCG)(LPS),。:BCG0.2ml/(5×106),10dLPS7.5μg/,16h、、[11,12]。BCGT,,,LPS,:NO、TNF-α、、。,BCGLPS,、,。2.2　,。10mg11μgLPS6d。,,。,,,,TNFa、IL-6,-6-,,,[13]。2.3　A(ConcanavalinA,ConA)ConA,、,T,,D-,,ConA,T,。ConA,20mg/kg。ConA,IL-10、IL-2、IL-12、TNF-a、γ-,[14]。ConA,,,,T。ConA,ConA,、,TNFα,[15]。2.4　,,。1%,0.4%。,,,,,、、。3　,,,,、,“”,,,。,,,,、DNA,,,,[16]。:[1]ShigaA,KakamuS,SugiyamaY,etal.Acutetoxicityofpierisin-1,acyto-toxicproteinfromPierisrapae,Inmouseandrat[J].JToxicolSci,2006,31(2):123.[2]FukudaT,MogamiA,TanakaH,etal.Y-40138,amultiplecytokinepro-ductionmodulator,protectsagainstd-galactosamineandlipopolysccharide-inducedhepatitis[J].LifeSci,2006,79(9):822.[3],,,.[J].,2005,21(1):42.[4],　.D-[J].,2008,18(4):11.[5]CoverC,LiuJ,FarhoodA,etal.Pathophysiologicalroleoftheacutein-flammatoryresponseduringacetaminophenhepatotoxicity[J].ToxicolAppl—1478—ChinJLabDiagn,October,2009,Vol13,No.10Pharmacol,2006,216(1):98.[6]LiuZX,HanD,GunawanB,etal.Neutrophildepletionprotectsagainstmurineacetaminophenhepatotoxicty[J].Hepatol,2006,43(6):1220.[7]XuJQ,LeeG,WangHM,etal.LimitedroleforCXCchemokinesinthepathogenesisofα-naphthylisothiocyanateinducedliverinjury[J].AMJPhysiolGastrointestLiverPhysiol,2004,287(3):G734.[8]HornTL,BhattacharjeeA,SchookLB,etal.Alteredhepatismrnaexpres-sionofapoptoticgenesduringdimethylnitrosamineexposure[J].ToxicolSci,2000,57(2):240.[9]YasudaM,OkabeT,1tohJ,etal.Differentiationofnecroticcelldeathwithorwithoutlysosomalactivation:applicationofacuteliverinjurymodelsin-ducedbycarbontetrachloride(CC14)anddimethylnitrosamine(DMN)[J].TheJournalHistochemistryandCytochemistry,2000,48(10):1331.[10],,,.[J].,2008,19(3):657.[11],　,,.[J].,1998,9(1):30.[12],,　,.[J].,2004,25(5):345.[13]KinWH,HongF,RadaevaS,etal.Stat1playsanessentialroleinLPS/D-galactosanine-inducedliverapoptosisandinjury[J].AMJPhysiolGastrointestLiverPhysiol,2003,285(4):G761.[14],,　,.A[J].,2008,7(5):297.[15]ErhardtA,BiburgerM,PapadopoulosT,etal.IL-10,regulatoryTcells,andKupffercellsmediatetoleranceinconcanavalinA-inducedliverin-juryinmice[J].Hepatol,2007,45(2):475.[16]ChoiJS,YoonTJ,KangKR,etal.GlycoproteinisolatedfromAcan-thopanaxsenticosusprotectedagainsthepatotoxicityinducedbyacuteandchronicalcoholtreatment[J].BiolPharmBul1,2006,29(2):306.(:2008-09-27):(200705389)＊:1007-4287(2009)10-1479-03bHLHOlig张晓璐,王宏芳,浦　昀,徐　坤,李　娟＊(,130021)　　,。(Oligodendrocytelin-eagegene,Olig)--(Basic-helix-loop-helix,bHLH),DNA,HLH。Olig。Olig,Olig(Periventricularleukomalacia,PVL)。1　OligOlig、,。OligOlig1,Olig2Olig3。Olig1/Olig2。Olig3,[1]。Olig1Olig2bHLH80%。,Olig1Olig2,[2]。,bHLHOlig1Olig2,。Olig1Olig2[1,3,4]。2　Olig,Olig1Olig29.5。,Olig1,Olig2。,。,Olig2。,12,Olig2。Olig110.5,Olig212。,。Olig,。,。13.514.5Olig2,11.5[5]。3　OligOlig。,—1479—　200910　13　10