低氧诱导因子在兔慢性缺血心肌中的表达趋势  

The trend of the expression of hypoxia-inducible factor-1α in ischemic rabbit myocardium subjected to long-term ischemia

作　　者：徐夏红[1] 王强[2] 董红燕[1] 姜波[2] 张中明[2] 

机构地区：[1]徐州医学院神经生物学研究中心,江苏徐州221002 [2]徐州医学院附属医院胸心外科,江苏徐州221002

出　　处：《徐州医学院学报》2010年第1期28-30,共3页Acta Academiae Medicinae Xuzhou

基　　金：国家自然科学基金(30672081);江苏省教育厅重点资助项目(03KJA320140)

摘　　要：目的探讨低氧诱导因子-1α（hypoxia-inducible factor-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West-ern Blot法测定HIF-1α蛋白表达。结果与非缺血组相比,兔心肌缺血早期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24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。Objective To investigate the trend of the expression of exogenous HIF-1α gene in rabbit myocardium subjected to long-term ischemia.Methods Animal models of myocardial ischemia were established with ligation of the left anterior descending coronary artery in China white rabbits（n=42）.The animals were divided into 7 groups according to different time points of ischemia.Myocardium from ischemic locus in each rabbit was obtained under anaesthesia at the corresponding（2nd,4th,6th,8th,10th and 12th） weeks.Expression of HIF-1α was assayed by immunohistochemical staining,real-time fluorescent quantitative reverse transcriptase-polymerase chain reaction（RT-Q-PCR） and western blot,respectively.Results From the onset of ischemia,there was a significant increase in exogenous HIF-1α mRNA and protein levels with a bimodal pattern of elevation： the levels of HIF-1α mRNA and protein reached their first peaks at the 2nd and 4th weeks（P〈0.01） respectively,and subsequently decreased.The deuto-peaks occurred at the 8th week（P〈0.05） of ischemia,followed by a decrease until the nadir at the 12th week,at which the HIF-1α expression levels still remained higher than the pre-ischemia levels（P〈0.01）.Conclusion The expression of exogenous HIF-1α is closely related to the oxygen supply in the infarcted loci.During the early stage of ischemia,upregulated HIF-1α is involved to maintain tissue oxygen homeostasis,while during chronic hypoxia,HIF-1α regulates the expressions of down-stream target genes and enhances myocardial oxygen supply,which in turn downregulates the expression of HIF-1α.

关 键 词：低氧诱导因子 心肌缺血 基因表达 兔 

分 类 号：Q786[生物学—分子生物学]