The Effect Of Recombinant Human Erythropoietin On Myocardial Protection In Rats With Myocardial Infarction

Objective: To study the effect of recombinant human erythropoietin (rHu-EPO) at different dosage on hemodynamic status, infarct size of left ventricle, myocardial apoptosis and Mfn2 protein expression in rats with myocardial infarction.Methods: 128 adult SD rats were divided randomly and equally into 4 groups: sham group (Sham), myocardial infarction group (MI), treatment group with high dose (MITH, loading dose 5000 IU/kg + high dose 1500 IU/kg for 1 week maintenance treatment), treatment group with low dose (MITL, loading dose + low dose 750 IU/kg for 1-week maintenance treatment). 24 hours and 2 weeks after operation, hemodynamic parameters, infarct size, myocardial apoptosis and Mfn2 protein expression were tested by carotid artery intubation, TTC staining, in situ terminal deoxynucleotidyl transferase(TdT)-dUTP nick-end labeling (TUNEL staining) and immunohistochemistry staining in each group, respectively.Results: 24 hours after operation, LVSP, LVEDP and±dp/dtmax in MI group were significantly worse than those in Sham group (P<0.05), while±dp/dtmax in the two treatment groups were remarkably better than those in MI group (P<0.05). The infarct size was similar in each group (P>0.05). Compared with Sham group, apoptosis index and Mfn2 protein expression of MI group remarkably increased (P<0.05), compared with MI group,apoptosis index and Mfn2 protein expression of MITH group and MITL group significantly decreased (P<0.05), there was no significant difference in apoptosis and Mfn2 protein expression between MITH group and MITL group (P>0.05). 2 weeks after operation, MI group showed significantly worse LVSP,LVEDP and±dp/dtmax than Sham group (P<0.05), while compared with MI group the two treatment group demonstrated remarkably improved±dp/dtmax (P<0.05) and significantly decreased infarct size (P<0.05).±dp/dtmax in MITL group were remarkably better than those in MITH group. Compared with Sham group, apoptosis index and Mfn2 protein expression of MI group remarkably increased (P<0.05), compared with MI group,apoptosis index and Mfn2 protein expression of MITH group and MITL group significantly decreased (P<0.05), there was no significant difference in apoptosis and Mfn2 protein expression between MITH group and MITL group (P>0.05).Conclusion: Loading dose of rHu-EPO immediately after myocardial infarction and maintenance treatment with less dose for one week can significantly reduce infarct size, protect cardiac function, decrease Mfn2 protein expression and reduce myocardial apoptosis. For maintenance treatment, rHu-EPO in low dose leads to better cardiac function than high dose. Maintenance treatment with high dose and low dose of erythropoietin shows no significant difference in both the effect of inhibiting apoptosis and regulating Mfn2 protein expression.