Abstract:
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 (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.
Results 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.
Conclusion 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.
Key words:
Recombinant Human Erythropoietin,
Myocardial ischemia/reperfusion injury,
Apoptosis,
Caspase-3,
Rabbit
Ying Pang, Mingting Liang, Jianqun Ma, Yong Yang, Jing Zhang. Protective effects and mechanisms of recombinant human erythropoietin on myocardial ischemia/reperfusion injury in rabbits[J]. Chinese Journal of Heart and Heart Rhythm(Electronic Edition), 2017, 05(01): 1-6.