低氧诱导因子在兔慢性缺血心肌中的表达趋势

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1、低氧诱导因子在兔慢性缺血心肌中的表达趋势作者：徐夏红，王强，董红燕　姜波，张中明【摘要】目的探讨低氧诱导因子-1α(hypoxia-induciblefactor-1α，HIF-1α)在兔缺血心肌的表达趋势。方法建立兔缺血心肌动物模型，于冠状动脉结扎前及术后第2、4、6、8、10、12周取各组动物缺血区心肌组织，采用荧光定量逆转录-聚合酶链反应(Q-RT-PCR)法测定心梗区HIF-1αmRNΑ的表达;应用免疫组化及WesternBlot法测定HIF-1α蛋白表达。结果与非缺血组相比，兔心肌缺血早

2、期HIF-1α表达水平显著增高(P<0.01)，HIF-1αmRNA及蛋白分别于第2及第4周达到高峰，持续约2～4周后，于第8周再次升高，并随之开始持续缓慢降低，但在缺血后第12周仍高于正常心肌表达量。结论HIF-1α的表达与心肌梗死区氧供关系密切，在心肌缺血早期，高表达HIF-1α参与了维持氧稳态及对低氧代谢的适应，在慢性缺氧期，随着HIF-1α调控多种下游靶基因表达，增加组织氧供使其表达渐显著降低。【关键词】低氧诱导因子;心肌缺血;基因表达;兔　　Abstract：ObjectiveTo

3、investigatethetrendoftheexpressionofexogenousHIF-1αgeneinrabbitmyocardium10subjectedtolong-termischemia.MethodsAnimalmodelsofmyocardialischemiawereestablishedwithligationoftheleftanteriordescendingcoronaryarteryinChinawhiterabbits(n=42).Theanimalswere

4、dividedinto7groupsaccordingtodifferenttimepointsofischemia.Myocardiumfromischemiclocusineachrabbitwasobtainedunderanaesthesiaatthecorresponding(2nd,4th,6th,8th,10thand12th)weeks.ExpressionofHIF-1αwasassayedbyimmunohistochemicalstaining,real-timefluore

5、scentquantitativereversetranscriptase-polymerasechainreaction(RT-Q-PCR)andwesternblot,respectively.ResultsFromtheonsetofischemia,therewasasignificantincreaseinexogenousHIF-1αmRNAandproteinlevelswithabimodalpatternofelevation:thelevelsofHIF-1αmRNAandpr

6、oteinreachedtheirfirstpeaksatthe2ndand4thweeks(P<0.01)respectively,andsubsequentlydecreased.Thedeuto-peaksoccurredatthe8thweek(P<0.05)ofischemia,followedbyadecreaseuntilthenadiratthe12thweek,atwhichtheHIF-1αexpressionlevelsstillremainedhighertha

7、nthepre-ischemialevels(P<0.01).ConclusionTheexpressionofexogenousHIF-1αiscloselyrelatedtotheoxygensupplyintheinfarctedloci.Duringtheearlystageofischemia,upregulatedHIF-1αisinvolvedtomaintaintissueoxygenhomeostasis,while10duringchronichypoxia,HIF-1α

8、regulatestheexpressionsofdown-streamtargetgenesandenhancesmyocardialoxygensupply,whichinturndownregulatestheexpressionofHIF-1α.　　Keywords:hypoxia-induciblefactor;myocardialischemia;geneexpression;rabbit　　低氧诱导因子(hypoxia-induciblefactor，HIF)是调节血