Effect of Recombinant Human Erythropoietin on Apoptosis of Neural Cells in Fetal Rats after Intrauterine Hypoxic-ischemic Injury

Objective To investigate the effect of recombine human erythropoietin (rhEPO) on apoptosis of neural cells in fetal rats after intrauterine hypoxic-ischemic injury. Methods Twenty SD rats on 19 days of pregnancy were divided into rhEPO (2500 U/kg, 5000 U/kg, 7500 U/kg) treated groups, ischemia-reperfusion (I/R) group and sham-operated group (4 rats in each group). Intrauterine hypoxic-ischemic injury of fetal rat was induced by bilateral occlusion of utero-ovarian artery for 20 min. rhEPO was injected into the rats in rhEPO treated group through the caudal vein 30 min before hypoxic-ischemic injury while saline was used in the other two groups. There was no hypoxic-ischemic injury in sham-operated group. The death rate of fetal rats was evaluated at 24 h after the operation, and then the brain samples of fetal rats were harvested. The expression of Caspase-3 protein was observed by immunohistochemistry. Neuroapoptosis was measured by TdT mediated dUTP-biotin nick end labeling (TUNEL) staining. Results Death rates of fetal rats in rhEPO treated groups decreased compared with the I/R group (P<0.05). Compared with the I/R group, there was less expression of copious Caspase-3 in rhEPO treated group (P<0.01). The expression of Caspase-3 was decreased in the rhEPO treated groups with the increase of rhEPO dose (P<0.01). Compared with the I/R group, the death rate of fetal rats in rhEPO treated groups decreased (P<0.05), the number of apoptosis cells also decreased obviously (P<0.01). The anti-apoptosis effect of 5000 U/kg rhEPO was similar to 7500 U/kg rhEPO, but better than 2500 U/kg rhEPO (P<0.01). Conclusion rhEPO can inhibit the apoptosis of fetal rat brain cells after intrauterine hypoxic-ischemic injury.