HIF-1α在七氟烷预处理减轻大鼠心肌缺血-再灌注损伤中的作用

Role of HIF-1α in the effect of sevoflurane-preconditioning on ischemia-reperfusion injury of isolated rat heart

目的研究低氧诱导因子1α(HIF-1α)在七氟烷预处理减轻离体大鼠心脏缺血-再灌注(I-R)损伤中的作用。方法 84只雄性SD大鼠随机均分为七组:假手术组(Sham组)、I-R组、七氟烷预处理组(S组)、七氟烷预处理+二甲氧乙二酰甘氨酸(DMOG)组(S+D组)、七氟烷预处理+3-(5′-羟基甲基-2′-呋喃基)-1-苯基吲哚(YC-1)组(S+Y组)、DMOG组(D组)和YC-1组(Y组)。应用Langendorff离体心脏灌流装置建立大鼠心肌I-R损伤模型,连续测定心功能指标,并取心肌测HIF-1α及半胱天冬氨酸蛋白酶3(Caspase-3)蛋白表达水平及HIF-1α目的基因的表达水平。结果与I-R组相比,S组、S+D组和S+Y组I-R损伤心功能的各项指标明显改善(P<0.05),HIF-1α表达水平显著升高(P<0.05),Caspase-3蛋白表达水平显著下降(P<0.05)。结论 HIF-1α促进七氟烷预处理对离体大鼠心脏I-R损伤的保护作用。

Objective To investigate the role of hypoxia inducible factor 1α（HIF-1α） in the effect of sevoflurane-preconditioning on ischemia-reperfusion（I-R） injury of isolated rat heart. MethodsEighty-four isolated hearts from male SD rats were equally divided into 7 groups of Sham （sham operation）, I-R （30 minutes of ischemia followed by reperfusion for 60 min）, S （sevofluranepreconditioning before I-R injury）, S＋D（sevoflurane preconditioning with tail vein injection of DMOG 20μg/g before I-R injury）, S＋Y（sevoflurane preconditioning with tail vein injection of YC-1 lmg/kgbefore I-R injury） ,D（tail vein injection of DMOG 20μg/g before I-R injury） and Y（tail vein injection of YC-1 lmg/kg before I-R injury）. Hemodynamics indexes were recorded and the expressions ofHIF-1α and Caspase-3 were determined by Western blot and RT-PCR at the end of reperfusion. Results Compared with group I-R, cardiac functional recovery was significantly improved（P〈0. 05）,the expression of HIF-1α was higher（P〈0. 05） and the expression of Caspase-3 was lower（P〈0. 05） in groups of S,S＋D and S＋Y after reperfusion. Conclusion The activation of HIF-1α may promotethe myocardial protective effect of sevoflurane-preconditioning on isolated rat heart with acute myocardial I-R injury.