特发性肺纤维化发病机制分析-analysis of pathogenesis of idiopathic pulmonary fibrosis.docxVIP

ThepathogenesisofIdiopathicpulmonaryfibrosisAbstractThepathogenesisofIdiopathicpulmonaryfibrosisAbstractBackground:Idiopathicpulmonaryfibrosis(IPF)isanunexplaineddiffuselungdisease,withrapidprogress,shortsurvivaltimeandhighmortalityrate.Withthedevelopmentandprogressinclinicalmedicine,anewclinicaldiagnosis,treatmentguidelinesandstandardswasannounedin2011.Followedbyalotofbasicresearchaboutthemechanismsandpotentialtreatment.ButthereisnoprogressontheeffectivetreatmentofIPF,exceptlungtransplantation.Thisworkresearchfromthreeparts,tryingtofindthepathogenesisofIPF.Part1:TherelationshipbetweenHLAgenepolymorphismandIPFObjective:WeinvestigatedtherelationshipbetweenHLA-A,BgenepolymorphismandIPFinaHanChinesepopulation.Method:Thegenefrequencyof67patientswithIPFwasdetectedusingaPCRSSPgroupingmethod.ThesevalueswerecomparedwiththoseaBoneMarrowBank(Shanghai,China)ofhealthysubjectsofidenticalracialoriginasthepatientgroup.Results:ThegenefrequencyofHLA-A*3(3.5%),HLA-B*15(10.2%),and-B*40(5.0%)oftheIPFgroupincreasedsignificantly(Pc0.05)comparedwiththatinthecontrolgroupHLA-A*3(1.0%),HLA-B*15(1.1%)and-B*40(0.8%).InvestigationofthelinkbetweentheHLA-Aand-BgeneshowedthegenefrequencyofHLA-A2B15tobe5.0%aswellas-A2B40(4.3%),-A11B15(5.0%),-A24B48(2.8%)whichweresignificantlyhigherthanthoseofthecontrolgroup(Pc0.05).Part2:BiologicalcharacteristicsofmyofibroblastsinIPFObjective:Toexplorethediffierenceonbiologicalcharacteristics,biomarkersandexocrineproteinbetweennormalhumansourceslungfibroblastsandIPFsourceslungmyofibroblasts.Method:Myofibroblastsandfibroblastswereisolatedfrom12IPFpatientsandlungtransplantdonors.Fibroblasts/myofibroblastswerecultured,identification,inducedandevaluatedusingimmunofluorescence,Westernblot,andAbstractThepathogenesisofIdiopathicpulmonaryfibrosisRT-PCR.Cytokineandchemokinelevels,includinghumanGM-CSF,IFN-γ,IL-10,IL-1β,IL-2,IL-4,IL-6,IL-8,MCP-1,andTNF-γweredeterminedusingLuminex.Results:BothoffibroblastsandmyofibroblastsexpressedFSP1butlackedexpressionofSPC.Upto30%ofthetrans