Recombinant human erythropoietin promotes angiogenesis in preterm rat models with periventricular white matter damage

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 randomly: the 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 group: 0.54±0.05 vs 0.42±0.05, 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 group: 0.85±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 group: 0.98±0.07 vs 0.85±0.06, P<0.05) and MVD(EPO group vs HI group: 4.71±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. Key words: Erythropoietin; Periventricular white matter damage; Hypoxia-ischemia; Immature rat, new born