左向右分流型肺动脉高压大鼠肺组织中microrna的表达谱及初步分析

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1、左向右分流型肺动脉高压大鼠肺组织中microRNA的表达谱及初步分析卢荣鑫，钟前进（400042重庆，第三军医大学大坪医院野战外科研究所心血管外科）[摘要]目的检测晚期肺动脉高压（pulmonaryhypertension，PH）大鼠肺组织中microRNA（miRNA）的表达，初步预测差异表达的microRNA调控的靶基因。方法4～5周龄健康雄性SPF级SD大鼠20只，体量90～110g，随机分成分流组（n=10）和对照组（n=10）。分流组采用套管法行右侧颈总动脉-颈外静脉分流术以建立左向右分流型肺动脉高

2、压模型,对照组行假手术，建立左向右分流型肺动脉高压大鼠模型12周后，取大鼠外周肺组织，运用microRNA表达谱芯片检测分流组和对照组大鼠肺组织microRNA的差异性表达。运用Miranda、TargetScan、PicTar软件预测可能调控的靶基因，实时定量PCR验证miR-98、miR-130b和miR-127等的表达。结果平均肺动脉压（mPAP）、肺动脉中膜厚度百分比（MT%）及右室肥厚指数（RVHI）均明显高于对照组（P<0.01），microRNA芯片结果提示：与对照组相比，在分流组大鼠肺组织中表

3、达明显上调的miRNA有30个（miR-122、miR-130b、miR-146b等），明显下的miRNA有7个（miR-382、miR-192、miR-29c等），RT-PCR结果与芯片结果一致。结论microRNA在左向右分流型肺动脉高压大鼠中表达存在差异，microRNA可能参与肺动脉高压大鼠肺血管的重构。[关键词]肺动脉高压；microRNA；肺血管重构DetectionandanalysisonmicroRNAExpressionProfilesinperipheralpulmonarytissue

4、sofratswithpulmonaryhypertension(PH)inducedbylefttorightshunt[Abstract]ObjectiveToinvestigatethedifferentialexpressionsofmicrRNAsinperipheralpulmonarytissuesofratswithpulmonaryhypertension(PH)inducedbylefttorightshunt.MethodsTwentymaleSDrats(aged4-5weeks，we

5、ighing95-110g)wererandomlydividedintoshuntgroupandcontrolgroup(10each).Ratsinshuntgroupunderwentrightcommoncarotidartery-externaljugularveinconnectiontoreproducePHmodeloflefttorightshunt,whileanimalsincontrolgrouponlyreceivedshamoperation.Theperipheralpulmo

6、narytissueswerecollected12weeksaftertheoperation.Quantitativereal-timePCRwereperformedtoconfirmtheresultsobtainedbymicroarrayanalysis.Meanwhile,theirtargetgeneswerepredictedbymiRNAtargetgenepredictionsoftwaressuchasMIRanda,TargetScanandPicTar.ResultsMeanpul

7、monaryarterialpressure(mPAP),rightventricularhypertrophyindex(RVHI),percentageofsmallpulmonaryarteriesmediathickness(MT%)weresignificantlyincreasedinshuntgroupcomparedwithcontrolgroupafter12weeksshunt(P<0.01).MicroRNAmicroassayshowedthat37microRNAswerediffe

8、rentiallyexpressedinshuntgroupandcontrolgroupincludingasetof30overexpressedmicroRNAsand7downexpressedmiRNAs.RT-PCRverifiedthatmiR-130b,miR-98wereupregulated,whilemiR-127wasdownregulatedinshuntgroup,whi