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《肝星狀細胞論文：熊果酸對大鼠肝星狀細胞nox亞基p47(phox)及其調(diào)控下游信號通路影響》由會員上傳分享，免費在線閱讀，更多相關內(nèi)容在行業(yè)資料-天天文庫。
1、肝星狀細胞論文：熊果酸對大鼠肝星狀細胞NOX亞基p47(Phox)及其調(diào)控的下游信號通路的影響【中文摘要】肝纖維化是肝臟慢性損傷后的一種普遍現(xiàn)象,最終導致細胞外基質(extracellularmatrix,ECM)在肝臟中過度沉積。瘦素是一個重要的促肝纖維化因子,它與HSC上的Ob受體結合后,引起Janus激酶(Januskinase,JAK)磷酸化及JAK-信號轉導及轉錄激活因子(signaltransducersandactivatorsoftranscriptionfactor,STAT)的活化。JAK還通過激活【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
