摘要
目的探讨人重组促红细胞生成素(rHuEPO)对离体心肌缺血再灌注损伤的保护机制。方法利用Langendorff离体心灌注模型,平衡30min,停搏液使心脏停跳90min,再灌注60min。24只Wistar大鼠随机分为3组:对照组、rHuEPO预处理组、rHuEPO灌注组。预处理组实验前24h腹腔给予rHuEPO5000u/kg,灌注组于缺血前10min灌注rHuEPO终浓度50u/mL的灌注液。观察各组再灌后脂质过氧化(MDA)含量、心肌凋亡及胞内Bcl-2、Bax蛋白表达情况,电镜观察心肌超微结构。结果预处理组和灌注组MDA含量较对照组显著减少(P<0.01);预处理组凋亡与对照组和灌注组相比显著减少(P<0.01),灌注组凋亡较对照组显著减少(P<0.01);预处理组心肌细胞Bcl-2含量显著高于对照组和灌注组(P<0.01),而Bax含量显著低于对照组和灌注组(P<0.01),灌注组和对照组心肌细胞Bcl-2和Bax含量差异无显著性(P>0.1);电镜示:对照组、灌注组和预处理组心肌肿胀程度,线粒体及肌丝等超微结构损伤依次小。结论rHuEPO改变Bcl-2/Bax平衡减少细胞凋亡、抑制氧自由基生成是其对离体心肌缺血再灌损伤保护的重要机制;rHuEPO预处理优于缺血前短时灌注,这可能与前者使抗凋亡蛋白充分表达有关。
[Objective] To discuss the mechanism of cardioprotective effect of rHuEPO on ischemia-repeffusion （I/R） injury in isolated rat hearts. [Methods] 24 rats were randomly divided into 3 groups： control group （Con）, rHuEPO preconditioning group （A） and rHuEPO peffusion group （B）. Isolated hearts studied by Langendorff model were subjected to perfusion for 30 min, ischemia for 90 min and reperfusion for 60 min. The rats of A were given 5 000 u/kg rHuEPO i.p. 24 hours before the experiment. The isolated hearts of B were perfused with Krebs- Henseleit buffer in the terminal concentration of 50 u/mL rHuEPO for 10 min just before ischemia. The MDA content were measured after reperfusion. Ischemia-induced apoptosis and the Bcl-2/Bax protein were detected by TUNEL and the immunochemical method, respectively. The ultrastructure of myocytes was observed by electron telescope. [Results] The MDA content of A and B were significantly lower than that of Con （P 〈0.01）. The apoptosis percentage of A was significantly lower than those of Con and B （P 〈0.01） while that of B was lower than Con （P 〈0.01）. The Bcl-2 content of A was significantly more than those of Con and B （P 〈0.01）, but the Bax content of A was lower than those of the other two （P 〈0.01）. There was no difference between B and Con in the content of Bcl-2/ Bax. The uhrastructure of A was protected better than those of B and Con after the reperfusion. [Conclusion] rHuEPO protects myocardium from I/R injury via reducing oxygen-derived free radicals and ischemia-induced apoptosis by changing the balance of Bcl-2/Bax. The effect of rHuEPO preconditioning against myocardial IfR injury is better than that of rHuEPO perfusion shortly before ischemia, possibly because anti-apoptosis proteins are expressed sufficiently via rHuEPO preconditioning.
出处
《中国现代医学杂志》
CAS
CSCD
北大核心
2006年第18期2729-2733,2737,共6页
China Journal of Modern Medicine
关键词
人重组促红细胞生成素
心肌保护
缺血再灌注损伤
预处理
心肌凋亡
recombinant human erythmpoietin （rHuEPO）
myocardial protection
ischemia-reperfusion injury
preconditioning
myocardial apoptosis
