toll样受体4在佐剂性关节炎模型大鼠外周血单核细胞中的表达及意义

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1、Toll样受体4在佐剂性关节炎模型大鼠外周血单核细胞中的表达及意义作者：张殿增，孟列素，王红英【摘要】目的研究佛氏完全佐剂性关节炎(AIA)大鼠外周血单核细胞(PBMC)对Toll样受体4(Toll-likereceptor4,TLR4)、TLR4mRNA的表达及其与关节炎评分的关系。方法流式细胞仪测定CD14+TLR4+细胞占CD14+细胞的比例和TLR4-PE的平均荧光强度(MIF)；Northernblot法测定PBMCTLR4mRNA的表达量。比较造模后15d与正常对照组和造模后25d时CD14+TLR4+/CD14+、MIF

2、及其TLR4mRNA表达量的差异，并用Mann-WhiteyU检验分析关节炎评分与TLR4MIF的相关性。结果在造模后15d，CD14+TLR4+/CD14+、TLR4MIF和PBMCTLR4mRNA的表达较正常对照组和造模后25d明显增高(P<0.01)，而且TLR4MIF与关节炎的评分有明显的相关性(15d：r=0.826，P<0.01；25d：r=0.688，P<0.05)。但造模后25d，CD14+TLR4+/CD14+、TLR4MIF和PBMCTLR4mRNA的表达与正常对照组和造模前相比无统计学意义(P&

3、gt;0.05)。结论TLR4与AIA发病有密切关系，提示固有免疫反应在类风湿性关节炎(RA)及其他自身免疫性疾病的发病中有重要的作用。【关键词】佐剂性关节炎；大鼠；Toll样受体4；外周血单核细胞13　　ABSTRACT:ObjectiveTodemonstratetheroleofinnateimmunityreactioninrheumatoidarthritisandotherautoimmunediseasesbystudyingtheexpressionoftoll-likereceptor4(TLR4)byperiphe

4、ralbloodmononuclearcell(PBMC)inratswithadjuvant-inducedarthritis(AIA)andanalyzingtherelationshipbetweenexpressionofTLR4byPBMCandscoreofarthritisseverity.MethodsBoththeproportionofCD14+TLR4+cellsinCD14+cellsandthemeanintensityoffluorescence(MIF)ofTLR4+cellswereanalyzedby

5、flowcytometry.ExpressionofTLR4mRNAbyPBMCwasdeterminedbyNorthernblot.CD14+TLR4+/CD14+ratio,TLR4MIFandexpressionofTLR4mRNAbyPBMCinthemodelgroupat15daysafterAIAwerecompared,respectively,withnormalcontrolgroupandmodelgroupat25days.ThecorrelationbetweenTLR4MIFandscoreofarthr

6、itisseveritywasanalyzedbyMann-WhiteyUtest.ResultsCD14+TLR4+/CD14+ratio,TLR4MIFandTLR4mRNAexpressioninmodelgroupat15daysafterAIAwereobviouslyincreasedcomparedwiththoseincontrolandmodelgroupsat25days(P<0.01),andagoodcorrelationbetweenTLR4MIFandscoreofarthritisseverityw

7、asobserved(15d:r=0.826,P<0.01;25d:r=0.688,P<0.05),butnosignificantdifferenceinmodelgroupat25daysafterAIA(P>0.05).ItindicatedthatTLR4participatedinthe13pathogenesisofrheumatoidarthritis.ConclusionTLR4expressedbyPBMCiscloselyassociatedwithpathogenesisandpathophys

8、iologyofrheumatoidarthritis,whichsuggeststhatinnateimmunityresponseplaysanimportantroleinpathogenesisofRAandot