肝星状细胞论文：熊果酸对大鼠肝星状细胞nox亚基p47(phox)及其调控下游信号通路影响

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1、肝星状细胞论文：熊果酸对大鼠肝星状细胞NOX亚基p47(Phox)及其调控的下游信号通路的影响【中文摘要】肝纤维化是肝脏慢性损伤后的一种普遍现象,最终导致细胞外基质(extracellularmatrix,ECM)在肝脏中过度沉积。瘦素是一个重要的促肝纤维化因子,它与HSC上的Ob受体结合后,引起Janus激酶(Januskinase,JAK)磷酸化及JAK-信号转导及转录激活因子(signaltransducersandactivatorsoftranscriptionfactor,STAT)的活化。JAK还通过激活【英文摘要】B

2、ackground:Hepaticfibrosisisauniversalphenomenonofchronicityliverinjurywhicheventuallyleadtotheextracellularmatrixdepositionintheliver.Leptinisanimportantfactorthatcanpromotetheliverfibrosisandcausephosphorylationofjanuskinase(JAK)andJAK-signaltransducersandactivationof

3、transcriptionfactor(STAT)bybindingwithobacceptorinHSCs.JAKactivatesreducedformofnicotinamide-adeninedinucleotidephosphateoxidase(NADPHoxidase,NOX)andthereduction-oxidation-sensitivecellssignalingpathwaysProteinkinaseB(AKT)andextracellularsignal-regulatedkinase(ERK)byge

4、neratingreactiveoxygenspecies(ROS).leadingtothesignalingcascadeandgeneexpressionrelatedtothefibrosisandinflammation.Previously,weperformedthestudythatUrsolicAcid(UA)couldsignificantlyimprovelivertissuestructureofhepaticfibrosisinvivo,andbetterthancolchicine.Itcouldinhi

5、bittheproliferationofHSCsandinducetheapoptosisofHSCsinvitro.PretreatmentwithUAcouldinhibitNOXsubunitp22PhoxandRaclmRNAandROSinducedbyleptinandactivationofnuclearfactor-KB,andsubsequentlyinducetheapoptosisofHSCs.Inthisstudy,wellobserveeffectsofUAonNOXsubunitp47phoandits

6、downstreamsignalingpathwayERK1/2inducedbyleptininHSCs,andexpressionofcollagen1.:ToexploretheeffectsofUAonNOXsubunitp47phoxanditsdownstreamsignalingpathwayERK1/2inducedbyleptininHSCs(HSC-T6),andproliferationofHSCsandexpressionofECM.Methods:HSC-T6intheexponentialgrowthph

7、aseweredevided:normalcontrolgroup;leptin(100ng/ml)treated;leptintreatedtogetherwithUA(50μM);leptintreatedtogetherwithJAKinhibitorAG490(50μM);leptintreatedtogetherwithNOXinhibitorDPI(20μM)andleptintreatedtogetherwithERKinhibitorPD98059(30μM).HSC-T6weretreatedwithmedicin

8、efor30minutesandmembraneproteinandphosphorylationproteinexpressionofp47phoxandERK1/2wereanalyzedwithwesternblotting;H