重组人促红细胞生成素在脑白质损伤新生鼠经细胞外信号调节激酶信号通路对血管内皮生长因子受体2的影响  

Impacts of Erythropoietin on Vascular Endothelial Growth Factor Receptor 2 by the Extracellular Signal-regulated Kinase Signaling Pathway in a Neonatal Rat Model of Periventricular White Matter Damage

作　　者：袁奇超[1] 蒋犁[1] 朱丽华[1] 虞大凡 

机构地区：[1]东南大学医学院附属中大医院儿科,南京210009

出　　处：《中国医学科学院学报》2016年第2期217-221,共5页Acta Academiae Medicinae Sinicae

摘　　要：目的探讨重组人促红细胞生成素在脑室周围白质损伤中颅内经细胞外信号调节激酶(ERK)信号通路对血管内皮生长因子受体2(VEGFR2)的影响。方法选取出生后4日龄SD大鼠,采用随机数余数分组法分为假手术组、缺氧缺血组和药物干预组。缺氧缺血和药物干预组幼鼠结扎右侧颈总动脉并吸入6%的氮氧混合气体2 h,假手术组幼鼠仅游离右侧颈总动脉。药物干预组脑室内给予重组人促红细胞生成素1次(0.6 IU/g体质量),假手术组和缺氧缺血组给予等量的生理盐水。用Western blot方法检测术后60、90 min脑组织中的ERK和磷酸化-ERK及术后2、4 d脑组织中的VEGFR2表达情况。结果术后60及90 min,缺氧缺血组磷酸化-ERK较假手术组显著增多(P<0.05),促红细胞生成素干预后磷酸化-ERK表达进一步上调(P<0.05)。术后2 d,缺氧缺血组和假手术组大鼠的VEGFR2表达差异无统计学意义,术后4 d缺氧缺血组VEGFR2表达增加(P<0.05),药物干预组VEGFR2的表达较缺氧缺血组显著增加(P<0.05)。结论促红细胞生成素可能通过影响颅内ERK信号通路调节VEGFR2的表达。Objective To explore the impacts of erythropoietin on vascular endothelial growth factor receptor 2（ VEGFR2） by the extracellular signal-regulated kinase（ ERK） signaling pathway in a neonatal rat model of periventricular white matter damage. Methods All of postnatal day 4 rats were randomized into three groups：the sham group [without hypoxia-ischemia（ HI） ], the HI group（ HI with saline administration）, and the erythropoietin（ EPO） group [HI with recombinant human erythropoietin（ rh-EPO） administration]. Rat pups underwent permanent ligation of the right common carotid artery,followed by 6% O2 for 2 hours or sham operation and normoxic exposure. Immediately after the HI,rats received a single intraventricular injection of rh-EPO（ 0. 6 IU/g body mass） or saline. ERK and phosphorylation-ERK were examined at 60 minutes and 90 minutes after operation,and VEGFR2 were detected at 2 and 4 days after operation by using Western blot. Results At60 minutes and 90 minutes after operation,the proteins of phosphorylation-ERK were significantly higher in HIrats than in the sham rats and significantly higher in HI ＋ EPO rats than in the HI rats（ P〈 0. 05）. Two days after operation,VEGFR2 was not significantly different between sham and HI rats. However, the proteins of VEGFR2 were increased after administration of rh-EPO（ P 〈0. 05）. Four days after operation,the proteins of VEGFR2 were significantly higher in HI rats than in the sham rats and significantly higher in HI ＋ EPO rats than in the HI rats（ P 〈0. 05）. Conclusion EPO may regulate VEGFR2 expression by affecting the intracranial ERK signaling pathways.

关 键 词：促红细胞生成素 脑室周围白质损伤 细胞外信号调节激酶 血管内皮生长因子受体2 

分 类 号：R722.1[医药卫生—儿科]