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促红细胞生成素可保护新生儿心脏的收缩功能免受缺血/再灌注损伤。

Erythropoietin protects the systolic function of neonatal hearts against ischaemia/reperfusion injury.

机构信息

Department of Cardiac Surgery, Faculty of Medical Science, State University of Campinas, Campinas, Brazil.

出版信息

Eur J Cardiothorac Surg. 2013 Jan;43(1):156-62. doi: 10.1093/ejcts/ezs254. Epub 2012 May 7.

Abstract

OBJECTIVES

The effect of erythropoietin (EPO) on neonatal hearts is not well understood. The current hypothesis is that EPO has protective effects against ischaemia-reperfusion when administered prior to ischaemia induction.

METHODS

Systolic and diastolic indices, as well as the Akt and extracellular-regulated kinase (Erk) signalling pathways, were studied in vivo using a neonatal pig heart model. Regional ischaemia was induced for 45 min by the ligation of the left anterior descending artery, followed by 90 min of reperfusion. The treatment groups consisted of: (i) untreated controls, (ii) treatment with EPO 3 min prior to ischaemia and (iii) treatment with EPO 24 h before ischaemia. Sophisticated myocardial contractility indices were assessed by pressure/volume loops of the left ventricle. The Akt and Erk pathways were evaluated via a western blot.

RESULTS

Elastance was found to be higher in the group receiving EPO 3 min prior to ischaemia. In addition, preload recruitable stroke work was higher for both groups receiving EPO prior to ischaemia when compared with controls. The time constant of the isovolumic relaxation and end-diastolic pressure-volume relationship did not differ between the three groups after 90 min of reperfusion. Furthermore, EPO treatment enhanced phosphorylation of Akt, but not Erk, and EPO-treated animals showed lower levels of apoptosis-related proteins.

CONCLUSIONS

EPO had a protective effect on neonatal systolic function after ischaemia/reperfusion injury, but no effect on diastolic function. This cardioprotective effect might be mediated by the activation of the Akt pathway.

摘要

目的

促红细胞生成素(EPO)对新生儿心脏的影响尚未完全清楚。目前的假说认为,EPO 在诱导缺血前给药时对缺血再灌注具有保护作用。

方法

使用新生猪心脏模型在体内研究收缩和舒张指数,以及 Akt 和细胞外调节激酶(Erk)信号通路。通过结扎左前降支诱导 45 分钟的区域性缺血,随后进行 90 分钟的再灌注。治疗组包括:(i)未处理的对照组,(ii)缺血前 3 分钟给予 EPO 治疗组,(iii)缺血前 24 小时给予 EPO 治疗组。通过左心室压力/容积环评估复杂的心肌收缩力指数。通过 Western blot 评估 Akt 和 Erk 通路。

结果

发现缺血前 3 分钟给予 EPO 的组弹性更高。此外,与对照组相比,在缺血前给予 EPO 的两组的预负荷可收缩功更高。在 90 分钟再灌注后,三组的等容松弛时间常数和舒张末期压力-容积关系没有差异。此外,EPO 治疗增强了 Akt 的磷酸化,但不增强 Erk 的磷酸化,并且 EPO 处理的动物显示出较低水平的凋亡相关蛋白。

结论

EPO 在缺血/再灌注损伤后对新生儿收缩功能具有保护作用,但对舒张功能没有影响。这种心脏保护作用可能是通过激活 Akt 通路介导的。

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