Recombinant human erythropoietin promotes angiogenesis in preterm rat models with periventricular white matter damage / 中华实用儿科临床杂志

ABSTRACT

Objective To evaluate whether recombinant human erythropoietin (rh-EPO) could increase the angiogenic responses in preterm rat models with periventricular white matter damage (PWMD).Methods Three-day postnatal rats were divided into 3 groups randomlythe sham group,the hypoxic-ischemic (HI) group and the recombinant human erythropoietin(rh-EPO)treatment group.Rat pups underwent permanent ligation of the right common carotid artery followed by 60 mL/L O2 for 4 h or sham operation and normoxic exposure.Immediately after the HI,rats received a single intraperitoneal injection of rh-EPO (5 U/g)or saline.Angiogenesis-related cells (CD34 + cells),microvessel density (MVD)and arteriovenous related genes (ephrinB2 and EphB4)were examined at 48 h and 96 h after operation.Results At 48 h after operation,the proteins of CD34 in HI rats increased compared with the sham rats (HI group vs Sham group0.54 ± 0.05 vs 0.42 ± 0.05,P ＜ 0.05).However,the MVD,the mRNA of ephrinB2 and EphB4 did not change (P ＞ 0.05).The proteins of CD34,the mRNA of ephrinB2 and EphB4 increased after rh-EPO treatment compared with HI rats.However,the MVD did not increase.As the proteins of CD34 increased further at 96 h after operation (HI group vs Sham group0.85 ± 0.06 vs 0.62 ± 0.06,P ＜ 0.05),the MVD (3.14 ± 1.21 vs 1.50 ± 1.04),ephrinB2 (7.51 ± 1.89 vs 1.28 ± 0.24) and EphB4 (4.58 ± 0.82 vs 1.21 ± 0.22) also increased (all P ＜ 0.05).And the proteins of CD34 increased after administration of rh-EPO(EPO group vs HI group0.98 ± 0.07 vs 0.85 ± 0.06,P ＜0.05) and MVD(EPO group vs HI group4.71 ± 1.38 vs 3.14 ± 1.21,P ＜0.05) were increased after administration of rh-EPO.However,the ephrinB2 and EphB4 did not increased after administration of rh-EPO at 96h time point.Conclusion Endogenous regenerative response is triggered in the damaged tissues and rh-EPO increases the angiogenesis in model rats with PWMD.