摘要
目的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。方法取新西兰大白兔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。结果血清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。结论 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。
Objective 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.Methods 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(1000 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.Results The Serum CK-MB concentration increased gradually with protraction of the ischemia and reperfusion time( P〈0.01).Before ischemia the serum CKMB 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 at60 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 a
作者
庞英
梁明亭
马建群
杨永
张静
Pang Ying;Liang Mingting;Ma Jianqun;Yang Yong;Zhang Jing(Department of Cardiology, Liaocheng People' s Hospital, Liaocheng , 252000, China;Department of Cardiology, The Affiliated Hospital of Shandong Academy of Medical Sciences, Jinan, 250031, China;Oepartnwnt of Pediatrics, Shenxian People's Hospital, Liaocheng ,252000, China)
出处
《中华心脏与心律电子杂志》
2017年第1期1-6,共6页
Chinese Journal of Heart and Heart Rhythm(Electronic Edition)