Mechanisms of vascular endothelial growth factor receptor 2 expression regulation by erythropoietin in a premature rat model of periventricular white matter damage / 中华围产医学杂志

ABSTRACT

Objective@#To explore the mechanisms of vascular endothelial growth factor receptor 2 (VEGFR2) expression regulated by recombinant human erythropoietin (rh-EPO) in a premature rat model of periventricular white matter damage. @*Methods@#Sprague-Dawley rats aged three days were randomly divided into five groups sham group without hypoxia-ischemia (HI), HI group (HI with saline administration), HI+erythropoietin (EPO) group, HI+erythropoietin receptor (EPOR) antagonist group and HI+EPO+EPOR antagonist group. Rat pups were either subjected to permanent ligation of the right common carotid artery and 6% O2+94% N2 for two hours (HI) or sham operated and exposed to normal air (sham). After the operation, rats in the HI+EPOR antagonist and HI+EPO+EPOR antagonist groups received a single intraventricular injection of EPOR antagonist (5 μl). Four hours after the operation, rats in the HI+EPO and HI+EPO+EPOR antagonist groups received a single intraperitoneal injection of rh-EPO (5 U/g). Western-blot was performed to detect EPOR, phosphorylated EPOR (p-EPOR), extracellular regulated protein kinases (ERK) and phosphorylated ERK (p-ERK) at 60 and 90 minutes after the models were established successfully, and also used to analyze the expression of VECFR2 on day 2 and 4. Analysis of variance and SNK test were used as statistical methods. @*Results@#At 60 and 90 minutes after model establishment, the expression of EPOR protein in rat brain tissues was increased in HI (1.717±0.206 and 1.416±0.242), HI+EPO (2.557±0.222 and 2.111±0.159) and HI+EPO+EPOR antagonist (1.547±0.170 and 1.452±0.250) groups as compared with that in sham group (1.095±0.182 and 0.751±0.136), that in HI+EPO group was higher than that in HI and HI+EPO+EPOR antagonist groups, and that in HI+EPOR antagonist group (1.088±0.160 and 1.020±0.174) was lower than that in HI group. All differences were statistically significant (F=30.154 and 20.265, both P<0.05). The expressions of p-EPOR, p-ERK and VEGFR2 in the five groups were consistent with the expression of EPOR, and the differences were also statistically significant (all P<0.05). In addition, the expression of VEGFR2 in HI+EPO+EPOR antagonist group was lower than that in HI group on day 4 (1.053±0.118 vs 1.439±0.074, F=54.248, P<0.05). No statistically significant difference in ERK expression was found among all groups at 60 or 90 minutes after modeling (F=1.117 and 0.734, both P>0.05). @*Conclusions@#ERK signaling pathways will be affected by EPO binding to EPOR. As a result, VEGFR2 expression was increased leading to enhanced angiogenesis in a premature rat model of periventricular white matter damage.