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促红细胞生成素对缺氧缺血性脑损伤保护作用机制的研究 被引量:14

Mechanism of Erythropoietin-induced hypoxic-ischemic brain injury protection
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摘要 目的构建新生儿缺氧缺血性脑病的经典动物模型,并分析在缺氧缺血条件下,促红细胞生成素(EPO)治疗前后胶质细胞谷氨酸运载蛋白2(EAAT2)表达情况。方法 108只出生72h的SD乳鼠随机分为六组:空白对照组、单纯缺氧组、单纯缺血组、缺氧缺血组、促红细胞生成素治疗组和生理盐水治疗组。缺氧缺血性脑病模型通过双侧结扎颈动脉并且缺氧处理2h建立。观察并记录不同实验组中乳鼠行为的变化。利用蛋白质印迹技术从蛋白质水平上分别检测不同实验组中EAAT2蛋白的表达情况。利用实时荧光定量聚合酶链反应(PCR)技术从mRNA水平上分别检测不同实验组中新生乳鼠的海马区、大脑皮层EAAT1、EAAT2的基因表达情况。结果模型呈现典型的缺氧缺血脑病特征。缺氧、缺血、缺氧缺血都可以导致海马组织、大脑皮层中EAAT1的mRNA水平及EAAT2表达量的降低。经过EPO治疗后,EAAT1及EAAT2的基因表达量明显上升。并且,大脑皮层中基因表达水平要高于海马组织中基因表达水平。结论 EAAT2表达量的下降可能是HIE发病的一个原因,EPO的疗效可能是通过上调EAAT2的表达量来实现。 Objective To assess the expression levels of excitatory amino acid transporter 2 (EAAT2) in classical rat model of hypoxic ischemic encephalopathy (HIE),and the expression level of that after erythropoietin (EPO) treatment. Methods Totally,108 postnatal 72 h SD rats were randomly assigned into six groups,including control,hypoxia,isehemia, hypoxiadschemia,EPO treatment,and saline treatment. A neonatal rat model of HIE by bilateral ligation of carotid artery and subsequent anaerobic treatment for 2 brs was constructed. The behavior of rats was recorded. The expression level of EAAT2 was assessed by Western blotting. Moreover,mRNA levels of EAAT1 and EAAT2 was measured using real time polymerase chain reaction. Results Typical HIE characteristics were observed on the models. The mRNA level of EAAT1 and expression level of EAAT2 was obviously reduced after hypoxia, ischemia, and hypoxia-ischemia. After treatment by EPO,the expression levels of EAAT1 and EAAT2 increased. Moreover, the gene expression levels in cortex were higher than that in hippocampe. Conclusion Reduced EAAT2 expression levels may be one reason for the development of HIE, which might also contribute to the curative effect of EPO.
出处 《中国儿童保健杂志》 CAS 2016年第8期825-828,834,共5页 Chinese Journal of Child Health Care
基金 深圳市基础研究计划项目(JCYJ20150402095641634)
关键词 促红细胞生成素 缺氧缺血性脑病 EAAT1 EAAT2 erythropoietin, hypoxic ischemic encephalopathy, excitatory amino acid transporter 1, excitatory amino acid transporter 2
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参考文献19

  • 1Tagin M, Abdel Hady H, ur Rahman S, et al~ Neuroprotec- tion for perinatal hypoxic ischemic encephalopathy in love and middle-income countries[J]. The Journal of Pediatrics, 2015,167(1) ,25-28.
  • 2Xu T, Li W, Liang Y, et al. Neuroprotective e{fects o~ electro acupuncture on hypoxic-ischemic encephalopathy in newborn rats Ass[J]. Pakistan Journal of Pharmaceutical Sciences, 2014,27(6), 1991-2000.
  • 3王钰,尹晓娟.促红细胞生成素在新生儿缺氧缺血性脑病中的研究进展[J].中国儿童保健杂志,2011,19(8):729-731. 被引量:4
  • 4Rocamonde B, Paradells S, Barcia JM, et al .- Neuroprotection of lipoic acid treatment promotes angiogenesis and reduces the glial scar formation after brain injury[J3. Neuroscience, 2012,224(1) :102 115.
  • 5Kim MS, Seo YK, Park HJ, et al ~ The neuroprotective effect of recombinant human erythropoietin via an antiapoptotic mechanism on hypoxic-ischemic brain injury in neonatal rats [,J]. Korean Journal of Pediatrics, 2010,53 (10) .. 898-908.
  • 6Sun Y, Zhou C, Polk P, et al : Mechanisms of erythropoietin- induced brain protection in neonatal hypoxia-ischemia rat model[,J]. Journal of Cerebral Blood Flow and Metabolism.. Official Journal of the International Society of Cerebral Blood Flow and Metabolism,2004,24 (2) :259-270.
  • 7Suzuki M, Nelson AD, Eickstaedt JB, et al: Glutamate en- hances proliferation and neurogenesis in human neural pro- genitor cell cultures derived from the fetal cortex[,J]. The European Journal of Neuroscience, 2006,24 (3) : 645-653.
  • 8Shigeri Y, Seal RP, Shimamoto K. Molecular pharmacology of glutamate transporters, EAATs and VGLUTs[,J~. Brain Research Reviews,2004,45 (3) :250-265.
  • 9Rao VL,Dogan A,Todd KG,et al. Antisense knockdown of the glial glutamate transporter GLT-1, hut not the neuronal glutamate transporter EAAC1, exacerbates transient focal cerebral ischemia-induced neuronal damage in rat brainEJ]. The Journal of Neuroseience: the Official Journal of the Soci ety for Neuroscience,2001,21(6) : 1876-1883.
  • 10Gilley JA, Kernie SG. Excitatory amino acid transporter 2 and excitatory amino acid transporter 1 negatively regulate calcium-dependent proliferation of hippocampal neural pro- genitor ceils and are persistently upregulated after injury [J]. The European Journal of Neuroscience,2011,34 (11) : 1712-1723.

二级参考文献33

  • 1王迎红,朱长连.促红细胞生成素通过早产儿血脑脊液屏障的观察[J].实用儿科临床杂志,2005,20(10):1005-1006. 被引量:18
  • 2刘海樱,徐英美,陈风展,郭锡熔.重组人促红细胞生成素对缺氧缺血新生鼠脑损伤学习记忆能力的保护[J].中国临床康复,2006,10(14):59-61. 被引量:1
  • 3Azzopardi DV, Strohm B, Edwards AD, et al. Moderate hypothermia to treat perinatal asphyxial encephalopathy[J]. N Engl J Med, 2009,361 (14): 1349-1358.
  • 4McPherson RJ, Juul SE. Recent trends in erythropoietinmediated neuroprotection[J].Int J Dev Neurosci , 2008,26 (1):103-111.
  • 5McPherson RJ, Demers EJ, Juul SE. Safety of high-dose recombinant erythropoietin in a neonatal rat model[J]. Neonatology,2007,91(1) :36-43.
  • 6Fauchere JC, Dame C, Vonthein R, et al. An approach to using recombinant erythropoietin for neuroprotection in very preterm infants[J]. Pediatrics, 2008,122(2) : 375-382.
  • 7Juul SE, MePherson RJ, Bauer LA, etal. A phase I/II trial of high-dose erythropoietin in extremely low birth weight infants: pharmaeokinetics and safet[J]. Pediatrics, 2008,122 (2) :383-391.
  • 8Bierer R,Peceny MC, Hartenberger CH, et al. Erythropoietin concentrations and neurodevelopmental outcome in preterm infants[J]. Pediatrics,2006,118(3) :e635-e640.
  • 9Brown MS, Eichorst D, Lala-Black B, et al. Higher cumulative doses of erythropoietin and developmental outcomes in preterm infants[J]. Pediatrics2009,124(4):e681-687.
  • 10Zhu C, Kang W, Xu F, et al. Erythropoietin improved neu rologic outcomes in newborns with hypoxic-ischemie enceph alopathy[J]. Pediatrics,2009,124(2) :e218-226.

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