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目的探讨促红细胞生成素(EPO)对糖尿病大鼠心肌组织血管内皮生长因子(VEGF)和EPO受体(EPOR)表达,以及心脏结构和功能的影响。方法雄性SD大鼠36只,随机分为正常对照组、糖尿病组和EPO组,均n=12。采用链脲佐菌素单次腹腔注射建立糖尿病动物模型,制模成功后,EPO组大鼠皮下注射EPO 1 000 IU·kg~(-1),每周1次,共12 wk。末次给药后d 7,尾静脉采血,检测血常规和血糖,流式细胞术测定外周血中内皮祖细胞(EPCs)数量,RT-PCR法分析VEGF和EPOR mRNA表达水平,Western blot技术检测VEGF和EPOR蛋白表达,免疫组化法检测左室心肌毛细血管密度,超声心动图检测心功能。结果与正常对照组比较,糖尿病大鼠EPCs数量、左心室心肌组织VEGF和EPOR蛋白和mRNA表达及毛细血管密度均显著减少(P<0.01),左室舒张末期内径(LVDd)和左室收缩末期内径(LVDs)明显增加(P<0.05),射血分数(EF)显著下降(P<0.01)。与糖尿病组相比,EPO组大鼠EPCs数量、左心室心肌组织VEGF和EPOR蛋白和mRNA表达及毛细血管密度均显著增加(P<0.01),EF值明显增加(P<0.05),LVDd和LVDs明显减少(P<0.05)。结论 EPO可增加糖尿病大鼠EPOR和VEGF蛋白和mRNA表达,增加EPCs数量和心肌新生血管的生成,改善心功能。
Objective To investigate the effect of erythropoietin (EPO) on the expression of vascular endothelial growth factor (VEGF) and EPO receptor (EPOR) and cardiac structure and function in diabetic rats. Methods Thirty-six male SD rats were randomly divided into normal control group, diabetic group and EPO group, all with n = 12. A single intraperitoneal injection of streptozotocin (STZ) was used to establish a diabetic animal model. After successful modeling, EPO rats were injected subcutaneously with 1 000 IU · kg -1 EPO once a week for 12 weeks. Blood samples were taken from the tail vein after the last administration, blood and blood glucose were measured, the number of endothelial progenitor cells (EPCs) in peripheral blood was measured by flow cytometry, VEGF and EPOR mRNA expression levels were analyzed by RT-PCR and VEGF And EPOR protein expression. The density of left ventricular capillary was detected by immunohistochemistry and the cardiac function was detected by echocardiography. Results Compared with the normal control group, the number of EPCs, the expression of VEGF and EPOR protein and mRNA and the density of capillary in left ventricular myocardium were significantly decreased (P <0.01), the left ventricular end-diastolic diameter (LVDd) and left ventricular end-systolic LVDs increased significantly (P <0.05), ejection fraction (EF) decreased significantly (P <0.01). Compared with diabetic group, the number of EPCs, the expression of VEGF and EPOR protein and mRNA and the density of capillary in EPO group were significantly increased (P <0.01), the EF value was significantly increased (P <0.05), LVDd and LVDs Significantly reduced (P <0.05). Conclusion EPO can increase the expression of EPOR and VEGF protein and mRNA in diabetic rats, increase the number of EPCs and the production of myocardial neovascularization, and improve the cardiac function.