Mechanisms of vascular endothelial growth factor receptor 2 expression regulation by erythropoietin in a premature rat model of periventricular white matter damage
10.3760/cma.j.issn.1007-9408.2018.06.008
- VernacularTitle: 重组人促红细胞生成素在早产儿脑白质损伤模型鼠中调控血管内皮生长因子受体2的机制
- Author:
Chunping JING
1
;
Lihua ZHU
2
;
Qichao YUAN
3
;
Huijuan LI
1
;
Li JIANG
1
Author Information
1. Department of Pediatrics, Zhongda Hospital, Medicine School, Southeast University, Nanjing 210009, China
2. School of Clinical Medicine, Jiangsu Health Vocational College, Nanjing 211800, China
3. Department of Pediatrics, People’s Hospital of Danyang, Danyang 212300, China
- Publication Type:Journal Article
- Keywords:
Leukomalacia, periventricular;
Infant, premature, diseases;
Erythropoietin;
Vascular endothelial growth factor receptor-2;
Disease models, animal
- From:
Chinese Journal of Perinatal Medicine
2018;21(6):401-407
- CountryChina
- Language:Chinese
-
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.
