基础医学与临床 ›› 2016, Vol. 36 ›› Issue (6): 817-821.

• 研究论文 • 上一篇    下一篇

重组人EPO通过减少自噬减轻大鼠心肌缺血再灌注损伤

郑巧,秦俭   

  1. 重庆医科大学附属第一医院
  • 收稿日期:2015-11-17 修回日期:2016-01-29 出版日期:2016-06-05 发布日期:2016-05-27
  • 通讯作者: 秦俭 E-mail:906165880@qq.com
  • 基金资助:
    重庆市卫生计生委医学科研项目

Recombinant human erythropoietin alleviates myocardial ischemia-reperfusion injury by reducing autophagy in rats

Qiao ZHENG1,   

  • Received:2015-11-17 Revised:2016-01-29 Online:2016-06-05 Published:2016-05-27

摘要: 目的 研究重组人促红细胞生成素(rhEPO)在大鼠心肌缺血/再灌注(I/R)损伤中的保护作用及其与自噬的关系。方法 将60 只SD大鼠随机分为假手术组(sham组)、缺血/再灌注组(I/R组)、rhEPO处理组(rhEPO组)、rhEPO +自噬激活剂雷帕霉素(Rap)处理组(rhEPO+Rap组)和雷帕霉素处理组(Rap组)。构建大鼠心肌I/R模型,术中监测血流动力学指标(LVSP、LVEDP、+dp/dtmax、-dp/dtmax);于再灌注结束后检测血清肌酸激酶(CK)和乳酸脱氢酶(LDH)活性;采用伊文氏蓝-TTC法检测心肌梗死面积;采用Western blot法检测自噬相关基因LC3、Beclin1的蛋白表达。结果 I/R组心功能明显减弱,血清CK、LDH含量增高,可见明显心肌梗死, LC3Ⅱ/ LC3Ⅰ、Beclin1蛋白表达上升(P < 0.01)。rhEPO处理后,心功能明显改善,CK、LDH含量减少,心梗面积缩小,LC3Ⅱ/ LC3Ⅰ、Beclin1蛋白表达下降(P < 0.01)。自噬激活剂雷帕霉素能削弱rhEPO的作用。结论 rhEPO减轻大鼠心肌缺血再灌注损伤的保护作用可能通过减少心肌自噬而完成。

关键词: 心肌缺血/再灌注, 重组人促红细胞生成素, 自噬

Abstract: Objective To investigate the protective effects of recombinant human erythropoietin(rhEPO)on rat myocardial ischemia-reperfusion(I/R)injury and the relationship with autophagy. Methods 60 SD rats were randomly divided into sham-operated group(sham group), ischemia-reperfusion group(I/R group), rhEPO treatment group(rhEPO group), rhEPO + autophagy activator Rapamycin treatment group (rhEPO +Rap group)and Rapamycin treatment group (Rap group). Myocardial ischemia- reperfusion(I/R)models were established, and hemodynamic indices(LVSP 、LVEDP、+dp/dtmax、-dp/dtmax)were monitored during the procedure. Serum creatine kinase (CK) , lactate dehydrogenase(LDH) of different groups were detected at the end of reperfusion. Myocardial infarct areas were measured by applying Evans blue and TTC staining respectively. The protein expressions of autophagy associated genes LC3 and Beclin1 in myocardium were identified by Western blot. Results Compared with sham group, I/R group showed weaker cardiac function,higher levels of serum CK、LDH and obvious myocardial infarct, LC3Ⅱ/ LC3Ⅰ, Beclin1 expressions were significantly increased(P < 0.01). rhEPO treatment can significantly improve cardiac function, reduce the serum levels of CK and LDH, reduce the myocardial infarct area, and significantly decrease the expressions of LC3Ⅱ/ LC3Ⅰ, Beclin1(P < 0.01). Autophagy activator rapamycin can weaken the effect of rhEPO .Conclusions rhEPO reduce autophagy plays an important role in the cardioprotection of rhEPO in rats model of myocardial ischemia- reperfusion injury.

Key words: myocardial ischemia- reperfusion, recombination human erythropoietin, autophagy

中图分类号: