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1、T-614治疗大鼠胶原诱导关节炎的机制研究杜芳，吕良敬，鲍春徳（上海交通大学医学院附属仁济医院风湿科，上海200001）摘要：FI的：探索T-614治疗RA的作用机制，以明确其是否具冇改善病情药物（DMARD）或免疫调节药物的特征；方法：建立大鼠胶原诱导关节炎（CIA）模型，分别给予T-614、MTX、尼美舒利或T-614+MTX联合治疗，比较齐组大鼠的发病悄况；X线检测骨质破坏情况；RealtimePCR检测外周血淋巴细胞和淋巴结细胞中IFN-丫、IL-4和IL-17的表达水平；蛋白芯片（Bio-plex）检测血清IL-ip>IL-6和TNF-a的含量;ELISA检测血清抗・II型胶原
2、抗体的含量。结果：与MTX相似，T-614对大鼠CIA的病情进程有显著的缓解作用，其关节炎评分、X线评分均显著减低；T-614能显著减少CIA血清IL-6含量，减少淋巴结细胞中IFN*和IL-17的表达水平，并减少CIA体内抗II型胶原抗体■特别是IgG2a型抗体的水平；结论：T-614能显著延缓CIA的发病进程、减轻关节损伤和骨质破坏程度，该病悄缓解效应与T-614减少细胞因子IL-6、IL-17和自身抗体的生成，调廿T细胞功能相关。关键词：风湿病；类风湿关节炎；Thl7细胞；胶原诱导关节炎模型中图分类号：R593.22TheraputicmechniasmofT-614intheCI
3、AratDUFang,LVLiangjing,BAOChunde(ShanghaiInstituteofRheumatology,RenjiHospital,ShanghaiJiaoTongUniversitySchoolofMedicine,Shanghai200001,China)Abstract:Objective:InthispapertoinvestigatethepotentialmechanismofT-614,anovelsyntheticsinthetreatmentofCIArat.Meterialsandmethods:Collagen-inducedarthrit
4、israts(CIA)weretreatedwithT-614(5or20mg/kg)daily,methotrexate(MTX,1mg/kg/3days)andnon-steroidanti-inflammatoryagent-nimesulide(10mg/kg)dailywereusedascontrols・AcombinationtherapygroupwastreatedbothT-614(10ing/kg,daily)andMTX(1mg/kg/3days).Hind-pawswellingandradiographicscoreswereevaluated,respect
5、ively.SerumcytokinelevelswereassessedbyBio-plexanalysis.QuantitativePCRwasusedtoevaluateexpressionofmRNAforinterferon-y,interleukin-4andinterleukin-17・Seruminterleukin-17andanti・typeIIcollagenantibodies(totalIgG、IgGl,IgG2a,IgG2bandIgM)werealsomeasuredbyenzyme-linkedimmunosorbentassays,respectivel
6、y.Results:OraladministrationofT・614couldinhibitpawswellingandofferedsignificantprotectionagainstartliritis-inducedcartilageandboneerosion,whichiscompatiblewithMTX・Collagen-inducedarthritisratstreatedwithT-614presenteddecreaseinbothmRNAexpressionofinterleukin-17inperipheralbloodmononuclearcellsand
7、lymphnodecells,aswellascirculatinginterleukin-17levelinadosedependentmanner.T-614alsoreducedtheserumlevelsoftumornecrosisfactor-a,interleukin-1卩andinterleukin-6.SynergisticeffectwasobservedinthecombinationofMTXandT-614
