吡格列酮对cxcl10介导的βtc6细胞凋亡及tlr4nf-κb表达的干预作用-effect of pioglitazone on cxcl 10 - mediated apoptosis of β tc6 cells and expression of tl r4 nf - κ b.docxVIP

TheexpressionofTLR4mRNAandproteindidn’tchangeafterinterveningwith0.1～1.0ng/mlCXCL10for12hours,butitwasincreasedwhenCXCL10was10.0ng/ml.AftertreatingwithCXCL101.0ng/mlfor24hours,TLR4mRNAandtheproteinexpressionwasalsoincreased.Whentheinterveningdurationprolongedto48hours,theexpressionofTLR4mRNAandtheproteinexpressionwasfurtherincreased，espectiallywith10.0ng/mlCXCL10for48hours.CXCL10mRNAandproteinexpressionwasincreasedinβTc6cellsinadose-andtime-dependentmanneraftercultivationwithCXCL10．TheactivationofNF-κBwasincreasedafterinterveningwith1.0～10.0ng/mlCXCL10for30minute.TheβTc6cells’NF-κBactivationcontinuesto24hoursafterinterveningwith10.0ng/mlCXCL10.Whentheinterveningdurationprolongedto48hours,theβTc6cellstreatingwithCXCL100.1～10.0ng/mldidn’tappearaforesaidsimilarchanges.NF-κBactivationinβTc6cellshadadose-andtime-dependentmanneraftercultivationwithCXCL10．AftertreatingwithCXCL100.1～1.0ng/mlfor24hours,CXCL10didn’tinducetheformationoftheDNAladderandapoptosis.FlowcytometryandDNAladderanalysisshowthattheβTc6cellstendedtobeapoptosisaftertreatingwithCXCL101.0ng/mlfor48hoursandCXCL1010.0ng/mlfor24～48hours.TheprotectioneffectsofPioglitazoneonthecellapoptosisofβTc6cellsinCXCL10stateasbelow：（1）CXCL10inducedβTc6cellsapoptosisandproliferationinhibitionwouldbepreventedbytreatingwith1.0umol/L～10.0umol/LPioglitazonefor24hoursinadvance,but0.1umol/LPioglitazonewouldnotpreventβTc6cellsfromapoptosis.（2）βTc6cellstreatingwith1.0umol/L～10.0umol/LPioglitazonefor24hoursinadvancewouldreducetheexpressionofTLR4/NF-κBinCXCL10state,but0.1umol/LPioglitazonewouldnotchangetheCXCL10inducedthecellTLR4/NF-κBsignalconduction.Conclusions：CXCL10withfiniteconcentrationcanchangeNF-κBactivation,butcan’taffectexpressionofTLR4，βcells’proliferationandapoptosisinashorttime.CXCL10withhighconcentrationcanchangetheexpressionofTLR4,βcells’proliferationandapoptosisinalongtime.TreatingwithPioglitazoneinoptimalconcentrationanddurationbeforehand,theTLR4expressionandNF-κBactivationinβcellsisreduced,βcellsapoptosisisprevented,