天津医药 ›› 2016, Vol. 44 ›› Issue (1): 63-66.doi: 10.11958/59073

• 实验研究 • 上一篇    下一篇

促红细胞生成素对慢性心力衰竭大鼠心肌细胞的抗凋亡作用及对AKT 蛋白表达的影响

许卫1 , 陈永权1 , 伍金雷1 , 刘欣1 , 陈晞明1△, 陈盛强2 , 孙卫文2   

  1. 1广州医科大学附属第三医院心内科 (邮编510150); 2广州医科大学附属第二医院
  • 收稿日期:2015-06-10 修回日期:2015-08-30 出版日期:2016-01-15 发布日期:2016-01-15
  • 通讯作者: △通讯作者 E-mail: 13903004891@163.com E-mail:13903004891@163.com
  • 作者简介:许卫 (1987), 男, 在读研究生, 住院医师, 主要从事冠心病防治相关研究
  • 基金资助:
    广东省科技厅项目 (2013B022000103)

Effects of erythropoietin on apoptosis and expression of AKT in rats of chronic heart failure

XU Wei 1 , CHEN Yongquan1 , WU Jinlei 1 , LIU Xin1 , CHEN Ximing1△, CHEN Shengqiang2 , SUN Weiwen2   

  1. 1 Department of Cardiology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou 510150, China; 2 The Second Affiliated Hospital of Guangzhou Medical College
  • Received:2015-06-10 Revised:2015-08-30 Published:2016-01-15 Online:2016-01-15
  • Contact: △Corresponding Author E-mail: 13903004891@163.com E-mail:13903004891@163.com

摘要: 摘要: 目的 观察促红细胞生成素 (EPO) 对慢性心力衰竭 (CHF) 大鼠心肌细胞的抗凋亡作用及对蛋白激酶 B (AKT) 蛋白表达的影响。方法 30 只成年雄性 SD 大鼠先按随机数字表法分为 2 组, 假手术 (Sham) 组 (n=6) 和模型(Model) 组 (n=24); 模型组采用腹主动脉缩窄术建立 CHF 模型, 术后 8 周存活 16 只, 再随机分为 EPO 组与对照(Control) 组各 8 只。EPO 组予以 3 000 U/kg EPO 腹腔注射, 3 次/周, 连续 4 周; Sham 组、 Control 组给予等量的生理盐水。分别在术后 4 周、 8 周、 12 周 (即给药 4 周) 行心脏彩超检查大鼠心功能。第 12 周末全部大鼠禁食 24 h 后处死, 观察心肌组织细胞形态、 心肌细胞凋亡及计算凋亡指数 (AI); 采用 Western blot 法检测心肌 P-AKT/AKT 蛋白表达情况。结果 超声心动图显示 Model 组 4 周时出现心室肥厚, 8 周时出现心力衰竭; EPO 干预 4 周后较 Control 组左室射血分数 (LVEF) 明显升高 (P < 0.05), 收缩末期室间隔厚度 (IVSs)、 收缩末期左心室后壁厚度 (LVPWs)、 舒张末期室间隔厚度 (IVSd)、 舒张末期左心室后壁厚度 (LVPWd) 明显降低 (P < 0.05)。EPO 组 AI 较 Control 组显著降低(23.87%±1.45% vs 35.58%±2.81%, P < 0.01); 与 Sham 组 (0.81±0.17) 比较, Control 组 (0.35±0.06) P-AKT/AKT OD 值明显降低, EPO 组 (1.61±0.16) 较 Control 组升高 (P < 0.01)。结论 EPO 可有效改善 CHF 大鼠的心功能, 抑制心肌细胞凋亡, 促进 AKT 的磷酸化。

关键词: 红细胞生成素, 心力衰竭, 心肌凋亡, AKT 蛋白

Abstract:  Objective To investigate the effects of erythropoietin (EPO) on myocardial apoptosis and protein kinase B (AKT) expression in rats of chronic heart failure (CHF). Methods Thirty male adult SD rats were randomly divided into two groups, sham-operated (Sham) group (n = 6) and model (Model) group (n = 24). The abdominal aortic coarctation was used to build CHF model. Sixteen survived rats after operation were randomly divided into two groups including EPO group and con⁃ trol (Control) group. EPO group was received 3 000 U/kg EPO intraperitoneal injection 3 times / week for 4 weeks, and Sham group and Control group were received same volume of normal saline. The echocardiography was used to evaluate cardiac function after 4 weeks, 8 weeks and 12 weeks of treatment. After 12 weeks, all rats were sacrificed after 24 h fasting. The cell morphology and myocardial apoptosis were observed, and apoptosis index (AI) was calculated. Myocardial P-AKT / AKT pro⁃ tein expression was detected by Western blot assay. Results Echocardiography showed that ventricular hypertrophy was found in model group after four weeks, heart failure 8 weeks. Compared with Control group, left ventricular ejection fraction (LVEF) was significantly higher after EPO intervention for 4 weeks (P < 0.05), systolic interventricular septum thickness (IVSs), end-systolic left ventricular posterior wall thickness (LVPWs), diastolic interventricular septum thickness (IVSd), af⁃ ter left ventricular end-diastolic wall thickness (LVPWd) were significantly lower (P < 0.05). The value of AI was significant⁃ ly lower in EPO group than that of Control group (23.87%±1.45% vs 35.58%±2.81%, P < 0.01). The OD value of P-AKT / AKT was significantly decreased in Control group (0.35±0.06) than that of Sham group (0.81±0.17), the value was significant⁃ ly increased in EPO group (1.61±0.16) than that of Control group (P < 0.01). Conclusion EPO can improve heart function, inhibit myocardial apoptosis, and promote pro-phosphorylation of AKT in rats with chronic heart failure.

Key words: rythropoietin, heart failure, cardiac apoptosis, AKT protein