Recombinant Human Erythropoietin Augments Neovascularization Responses in a Neonatal Rat Model of Premature Brain Damage by Phosphatidylinositol 3 Kinase/Akt Pathway

作     者：Da-Fan Yu Li-Hua Zhu Li Jiang Yu Da-Fan;Zhu Li-Hua;Jiang Li

作者机构：Department of Clinical Medcine Medical School of Southeast University Jiangsu 210009 China 2Department of Pediatrics Zhongda Hospital Southeast University Nanjing Jiangsu 210009 China 

出 版 物：《Chinese Medical Journal》 (中华医学杂志（英文版）)

年 卷 期：2017年第130卷第7期

页      面：854-858页

核心收录：

学科分类：1002[医学-临床医学] 100202[医学-儿科学] 10[医学] 

基　　金：supported by a grant from the National Natural Science Foundation of China 

主　　题：Erythropoietin Hypoxia-ischemia Neovascularization Premature Brain 

摘      要：Background：Recombinant human-erythropoietin （rh-EPO） has therapeutic efficacy for premature infants with brain damage during the active rehabilitation and anti-inflammation.In the present study,we found that the rh-EPO was related to the promotion ofneovascularization.Our aim was to investigate whether rh-EPO augments neovascularization in the neonatal rat model of premature brain damage through the phosphatidylinositol 3 kinase （PI3K）/protein kinase B （Akt） signaling pathway.Methods：Postnatal day 5 （PD5）,rats underwent permanent ligation of the right common carotid artery and were exposed to hypoxia for 2 h.All the rat pups were randomized into five groups as follows：（1） control group;（2） hypoxia-ischemic （HI） group;（3） HI ＋ LY294002 group;（4） HI ＋ rh-EPO group;and （5） HI ＋ rh-EPO ＋ LY294002 group.The phospho-Akt protein was tested 90 min after the whole operation,and CD34,vascular endothelial growth factor receptor 2 （VEGFR2）,and vascular endothelial growth factor （VEGF） were also tested 2 days after the whole operation.Results：In the hypoxic and ischemic zone of the premature rat brain,the rh-EPO induced CD34＋ cells to immigrate to the HI brain zone （P 〈 0.05） and also upregulated the VEGFR2 protein expression （P 〈 0.05） and VEGF mRNA level （P 〈 0.05） through the PI3K/Akt （P 〈 0.05） signaling pathway when compared with other groups.Conclusions：The rh-EPO treatment augments neovascularization responses in the neonatal rat model of premature brain damage through the PI3K/Akt signaling pathway.Besides,the endogenous EPO may exist in the HI zone of rat brain and also has neovascularization function through the PI3K/Akt signaling pathway.