促红细胞生成素对急性心肌梗死大鼠的心肌HIF-1α与Survivin表达的影响

Effect of erythropoietin on the expression of HIF-1αand Survivin in myocardium of rats with acute myocardial infarction

目的探讨促红细胞生成素对急性心肌梗死(AMI)大鼠心肌缺氧诱导因子-1α(HIF-1α)与生存素(Survivin)蛋白表达的影响。方法将36只健康雄性SD大鼠随机分为假手术组、急性心肌梗死组和促红细胞生成素(EPO)治疗组。急性心肌梗死组及EPO治疗组通过冠状动脉左前降支结扎建立急性心梗模型。模型建立4周后,利用心脏超声评价心功能,原位末端凋亡法(TUNEL)检测心肌细胞凋亡情况,采用免疫组织化学方法与Western blot方法检测各组大鼠心梗区域心肌HIF-1α与Survivin蛋白的表达。结果与急性心肌梗死组大鼠相比,EPO治疗组大鼠心功能明显改善,左室射血分数明显增加,左室舒张末期内径(LVEDD)明显缩小(P<0.01)。急性心肌梗死组大鼠比假手术组心肌细胞凋亡数明显升高,心肌HIF-1α蛋白表达量显著升高,Survivin蛋白表达量显著降低,而EPO治疗组大鼠比急性心肌梗死组心肌细胞凋亡数明显降低,心肌HIF-1α蛋白表达量显著降低,Survivin蛋白表达量显著升高(P<0.01)。结论降低HIF-1α蛋白表达与上调Survivin蛋白表达可能是促红细胞生成素抑制急性心肌梗死大鼠心肌细胞凋亡的机制之一。

Objective To investigate the effect of erythropoietin（EPO） on the expression of hypoxia inducible factor 1- alpha（HIF-1 α ） and Survivin protein in myocardium of rats with acute myocardial infaretion（AMI）. Methods 36 healthy male SD rats were randomly divided into sham group, acute myocardial infarction group and erythropoietin（EPO） treatment group. An acute myocardial infarction model was established by ligation of the left anterior descending coronary artery. 4 weeks after the establishment of the model, cardiac function was evaluated by echocardiography, and apoptosis was assessed by TdT-mediated dUTP Nick-End Labeling（TUNEL）. Immunohistoehemistry and Western blot were used to detect the expression of HIF-1α and Survivin proteins in myocardium of acute myocardial infarction rats. Results Compared with the acute myocardial infarction group, the heart function was improved, the left ventricular ejection fraction was increased significantly, and the left ventrieular end diastolic diameter（LVEDD） was reduced significantly in EPO treatment group（P〈0.01）. Compared with the sham group, the number of apoptotic cells in myocardium of AMI group was increased significantly, the expression level of HIF-1α protein was increased significantly, and the expression level of Survivin protein was decreased significantly（P〈0.01）. Compared with the acute myocardial infarction group, the number of apoptotic cells in the EPO treated group was decreased significantly, the expression level of HIF-1 alpha protein was decreased significantly, and the expression level of Survivin protein was increased significantly（P〈0.01）. Conclusion The downregulating the expression of HIF-1 alpha protein and up-regulating the expression of Survivin protein might be related to the mechanism of erythropoietin inhibiting cardiomyocyte apoptosis in acute myocardial infarction rats.