机构地区:[1]东南大学附属中大医院儿科,南京210009 [2]江苏卫生健康职业学院临床医学院,南京211800 [3]江苏省丹阳市人民医院儿科,212300
出 处:《中华围产医学杂志》2018年第6期401-407,共7页Chinese Journal of Perinatal Medicine
基 金:国家自然科学基金(81601355、81771628)
摘 要:目的探讨在早产儿脑白质损伤模型鼠脑血管生成中,重组人促红细胞生成素(recombinant human erythropoietin, rh-EPO)调控血管内皮生长因子受体2( vascularendothelial growth factor receptor 2, VEGFR2) 表达的可能机制。方法选取3日龄Sprague Dawley仔鼠,采用随机数余数分组法分为假手术组、缺血缺氧组、缺血缺氧+促红细胞生成素(erythropoietin,EPO)组、缺血缺氧+EPO受体( erythropoietin receptor, EPOR )拈抗剂组、缺血缺氧+EPO+EPOR拮抗剂组。假手术组仔鼠仅游离右侧颈总动脉。缺血缺氧组仔鼠结扎右侧颈总动脉,并吸人氮氧混合气体2h。缺血缺氧+EPO组、缺血缺氧+EPO+EPOR拮抗剂组结扎后4h腹腔内给予rh—EPO5U/g。缺血缺氧+EPOR拈抗剂组、缺血缺氧+EPO+EPOR拮抗剂组,结扎后脑室内给予EPOR拮抗剂5μl,其余组均给予等量生理盐水。采用蛋白质印迹技术检测分组处理完成后60和90min脑组织中EPOR和磷酸化EPOR(phosphorylated—EPOR,p-EPOR)、总细胞外信号调节激酶( extracellular regulated protein kinases, ERK )和磷酸化ERK(phosphorylated—ERK,p-ERK)及分组处理完成后2、4d脑组织中的VEGFR2表达情况。多组间数据比较采用单因素方差分析,组间两两比较采用SNK检验。结果分组处理完成后60和90min,仔鼠脑组织EPOR蛋白表达在假手术组呈较低水平(分别为1.095±0.182和0.751±0.136);在缺血缺氧组(1.717±0.206和1.416±0.242)、缺血缺氧+EPO组(2.557±0.222和2.111±0.159)和缺血缺氧+EPO+EPOR拮抗剂组(1.547±0.170和1.452±0.250)表达增加,高于假手术组;在缺血缺氧+EPO组高于缺血缺氧组和缺血缺氧+EPO+EPOR拮抗剂组;在缺血缺氧+EPOR拈抗剂组(1.088±0.160和1.020±0.174)低于缺血缺氧组;差异均有统计学意义(F值分别为30.154和20.265,P值均〈0.05)。p-EPOR和pObjective 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% 02+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 μ l). 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,
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