观察重组人促红细胞生成素(recombinant human erythropoietin，rhEPO)对心肌缺血再灌注损伤(myocardial ischemia/reperfusion injury，MI/RI)兔心肌细胞凋亡及凋亡关键蛋白酶半胱氨酸蛋白酶-3(Caspase-3)表达的影响，探讨rhEPO对兔MI/RI损伤的保护作用及其机制。

取新西兰大白兔16只，随机分为对照组(MI/RI组)和药物组(rhEPO组)。结扎兔左冠状动脉前降支制备MI/RI模型。rhEPO组于结扎左冠状动脉前降支的同时注入rhEPO(1 000 U/kg)，对照组注入等量的0.9%氯化钠注射液。分别于缺血前、缺血60 min、再灌注60 min和再灌注180 min检测肌酸激酶同工酶MB(CK-MB)的浓度；取缺血区心肌组织，检测其凋亡指数以及凋亡关键蛋白酶Caspase-3的表达水平；制作光镜和电镜标本，观察心肌组织大体形态结构和超微组织结构。

血清CK-MB浓度随缺血及再灌注时间延长而增加(P<0.01)；缺血前rhEPO组与MI/RI组血清CK-MB浓度差异无统计学意义(P>0.05)；缺血60 min、再灌注60 min、再灌注180 min时，rhEPO组血清CK-MB浓度均显著低于MI/RI组(均P<0.01)。与MI/RI组相比，rhEPO组缺血区心肌细胞凋亡指数显著下降(P<0.01)，凋亡关键蛋白酶Caspase-3表达水平亦显著下降(P<0.01)。rhEPO组心肌组织细胞大体形态结构及超微组织结构损伤均较MI/RI组减轻。

rhEPO对兔MI/RI具有明显保护作用，其机制与稳定心肌细胞膜结构、减少心肌酶释放和抑制心肌细胞凋亡有关；rhEPO抑制心肌细胞凋亡可能通过抑制Caspase-3蛋白表达发挥作用。

To investigate the influence of Recombinant Human Erythropoietin (rhEPO) on cardiac myocyte apoptosis and the expressing level of Caspase-3 protease which is critical in apoptosis in Myocardial ischemia/reperfusion injury(MI/RI) rabbits in order to explore the protective effects of rhEPO on MI/RI rabbit and its mechanisms of action.

Sixteen New Zealand rabbits were randomly divided into two groups: control group( MI/RI group) and drug group (rhEPO group). Rabbits were subjected to descending coronary artery(LAD) occlusion to establish rabbit MI/RI models.When the left anterior descending coronary arteries were ligated, RhEPO (1 000 U/kg) were injected in rabbits of rhEPO group, the rabbits of control group were injected saline equivalently. Serum abstracted from the blood for testing the concentration of CK-MB at the following points: 5 minutes before occlusion, 60 minutes after occlusion, 60 minutes and 180 minutes after reperfusion; At 180 minutes after reperfusion, The apoptotic index of the corresponding ischemic myocardial cell and the level of Caspase-3 in ischemic region were tested; The specimens of light microscope and electron microscopy were made to observe the general myocardial tissue morphosis and ultramicro organizational structure.

The Serum CK-MB concentration increased gradually with protraction of the ischemia and reperfusion time(P<0.01). Before ischemia the serum CK-MB concentration were no significant difference between rhEPO group and the MI/RI group(P>0.05). The increased level of CK-MB concentration in rhEPO group were markedly lower than those in the I/R group at 60 minutes after ischemia, 60 minutes after reperfusion and 180 minutes after reperfusion.The difference was statistically significant(P<0.01). Compared to the MI/RI group, both the ischemic myocardial apoptotic index and the expressing level of Caspase-3 in rhEPO group decreased significantly(P<0.01). The impaired changes of the general morphosis and the ultrastructure at MI/RI areas in the MI/RI group were severer than that in the rhEPO group.

RhEPO has visible protective effects on the MI/RI rabbits. The mechanism of cardioprotection may be associated with stabilizing the myocardium cell membrane structure to decrease the release of myocardial enzyme and inhibit cardiac myocyte apoptosis. RhEPO can inhibit the cardiac myocyte apoptosis induced by ischemia/reperfusion injury through downregulation of the Caspase-3 protein expression.