促红细胞生成素在缺氧缺血性脑病新生鼠模型中的神经保护作用被引量：8

Protective Effect of Erythropoietin on Neurology of Hypoxic-Ischemic Encephalopathy Model in Neonatal Rats

下载PDF

导出

摘要目的探讨促红细胞生成素（EPO）在缺氧缺血性脑病（HIE）新生鼠模型中的神经保护作用。方法新生鼠HIE模型为7日龄新生鼠，结扎右侧颈总动脉，在缺氧环境下（氧体积分数为80mL／L）放置2h。实验分为假手术组、对照组和EPO组。从手术前2d开始，对照组注射磷酸盐酸缓冲液（PBS），EPO组注射EPO4000U／（kg·d），持续注射9～16d。通过测脑质量、脑损伤比率、姿势反射实验观察EPO疗效。体外实验利用神经干细胞系C17．2，在无血清条件下培养，体外模拟缺血环境，诱导细胞凋亡，利用流式细胞技术检测Anexin V，研究EPO对C17．2的保护作用。结果对照组脑质量、脑损伤比率明显大于假手术组（Pa〈0．05）。姿势反射实验对照组明显低于假手术组（P〈0．05）。EPO处理后，脑质量明显提高，脑损伤比率明显减小，姿势反射实验正常百分率提高（Pa〈0．05）。体外实验，用流式细胞技术检测Anexin V，发现EPO可有效减少神经细胞凋亡（P〈0．05）。结论EPO在HIE中具有神经保护作用，且有抗神经于细胞凋亡作用。 Objective To study the neuroprotective effect of erythropoietin （EPO） on neonatal rats model with hypoxia - isehemia encephalopathy （HIE）. Methods HIE was induced in rats on 7th day of postnatal age by ligatian of right common carotid artery, followed by 2 h of hypoxia （80 mL/L 02 ）. The subjects were divided into sham - operated group ,control group and EPO group. EPO 4 000 U/（ kg · day） was injected daily from day 2 pre -surgery for 9 to 16 days and PBS was injected in the control group. The neuroprotective effect of EPO on HIE model was detected by brain weight, the difference in weights between the ipsilateral （right） and contralateral （left） brain and the function test. In vitro study, the neural progenitor cell line C17.2 under gone apoptosis following an ischemia - like metabolic inhibition. The effect of EPO on the cell line ischemia modle 17.2 was evaluated by detecting Annexin V with flow cytometry. Results The significant and sustained brain injury in the hypoxia - ischemia and vehicle - treated group was observed and measured by reduction in relative weights of ipsilateral to contralateral and compromised sensorimotor functions in response to postural reflex test, compared with those of sham -operated animals（ Pa 〈0.05 ）. Treatment with EPO significantly reduced severity of brain injury, indicated by increasing ipsilateral brain relative weight and neuron density （ P 〈 0.05 ）. Recoveries of sensorimotor functions and histomorphology were observed in animals that received EPO. EPO increased cell viability and protected brain cells against apoptosis damage （ Pa 〈 0.05 ）. Conclusion EPO possesses anti - apoptosis functions and has effective in neuroprotection against brain injury induced by hypoxia - ischemia in neonatal rats.

作者夏文杰杨默罗广平付涌水汪传喜张丽蓉

机构地区广州血液中心器官移植配型中心香港大学儿科学系广东药学院病理生理学教研室

出处《实用儿科临床杂志》 CAS CSCD 北大核心 2007年第6期416-418,共3页 Journal of Applied Clinical Pediatrics

基金广州市科技局科技计划项目资助(2006J-1C0271)

关键词促红细胞生成素类神经保护鼠新生缺氧缺血脑 erythropoietin neuroprotection neonatal rats hypoxia - ischemia encephalopathy

分类号 R722.1 [医药卫生—儿科]

引文网络
相关文献

参考文献14

1Ambalavanan N, Carlo WA, Shankaran S,et al. Predicting outcomes of neonates diagnosed with hypoxemic- ischemic encephalopathy[ J]. Pediatrics, 2006,118 (5) :2084 - 2093.
2Perlman JM. Summary proceedings from the neurology group on hy poxic - ischemic encephalopathy [ J ]. Pediatrics, 2006,117 (3 Pt 2 ) :S28 - S33.
3Tovari J, Gilly R, Raso E, et al. Recombinant human etythropoietin alpha targets intratumoral blood uessels, improving chemotherapy in human enograft models[J]. Cancer Res, 2005,65(16) :7186 -7193.
4Milano M, Collomp R. Erythropoietin and neuroprotection: A therapeutic perspective [ J]. J Oncol Pharm Pract, 2005,11 (4) :145 -149.
5Bemaudin M, Marti HH, Roussel S,et al. A potential role for erythropeietin in focal permanent cerebral ischemia in mice [J]. J Cereb Blood Flow Metab ,1999 ,19 ( 6 ) : 643-651.
6Siren AL, Knerlich F,Poser W,et al. Etythropoietin and erythropoietin receptor in human ischemic/hypoxic brain [ J ]. Acta Neuropathol(Berl), 2001,101(3) : 271 -276.
7Wen TC, Rogido M, Genetta T, et al. Permanent focal cerebral ischemia activates erythropoietin receptor in the neonatal rat brain [ J]. Neurosci Lett, 2004,355 : 165 - 168.
8Ren JM, Finklestein SP. Growth factor treatment of stroke [ J ]. Curr Drug Targets CNS Neurol Disord, 2005,4 (2) : 121 - 125.
9Xia WJ, Yang M, Fok TF. Partial neuroprotective effect of pretreatment with tanshinone ⅡA on neonatal hypoxia - ischemia brain damage [ J ].Pediatr Res , 2005,58(4): 784-790.
10Rice JZ, Vannucci RC, Brierhey JB. The influence of immaturity on hypoxic- ischemic brain damage in the rat [ J ]. Ann Neurol, 1981,9:131 - 141.

二级参考文献12

1Digicaylioglu M, Bichet S, Marti HH, Wenger RH, Rivas LA,Bauer C, et al.Localization of specific erythropoietin binding sites in defined areas of the mouse brain[J]. Proc Natl Acad Sci U S A. 1995, 92(9): 3717-3720.
2Sakanaka M, Wen TC, Matsuda S, Masuda S, Morishita E, Nagao M, et al. In vivoevidence that erythropoietin protects neurons from ischemic damage [J]. Proc Natl Acad SciU S A. 1998, 95(8): 4635-4640.
3Wen TC, Sadamoto Y, Tanaka J, Zhu PX, Nakata K, Ma YJ,et al. Erythropoietinprotects neurons against chemical hypoxia and cerebral ischemic injury by up-regulatingBcl-xL expression [ J]. J Neurosci Res. 2002, 67 (6): 795-803.
4Spandou E, Papoutsopoulou S, Soubasi V, Karkavelas G, Simeonidou C, KremenopoulosG, et al. Hypoxia-ischemia affects erythropoietin and erythropoietin receptor expressionpattern in the neonatal rat brain [J]. Brain Res. 2004, 1021(2): 167-172.
5Spandou E, Soubasi V, Papoutsopoulou S, Karkavelas G, Simeonidou C, Kaiki-Astara A,et al. Erythropoietin prevents hypoxia/ischemia-induced DNA fragmentation in anexperimental model of perinatal asphyxia [J]. Neurosci Lett. 2004, 366( 1 ): 24-28.
6Hang Y-K. Clinical diagnosis and clinical grading of neonatal hypoxic-ischemicencephalopathy ( in Chinese) [ J ]. Chin J Pediatr, 1997, 35 (2): 99-100.
7Chen L-Y, Wang X-M, Meng S-Z, Hang Y-K. Study on hypoxicischemic encephalopathy infull-term neonates ( in Chinese) [J].Chin J Med Comput Imaging, 1999, 5( 1 ): 47-50.
8Maier RF, Bohme K, Dudenhausen JW, Obladen M. Cord blood erythropoietin inrelation to different markers of fetal hypoxia [J].Obstet Gynecol, 1993, 81(4): 575-580.
9Juul SE, Harcum J, Li Y, Christensen RD. Erythropoietin is present in thecerebrospinal fluid of neonates [ J]. J Pediatr, 1997,130(3): 428-430.
10Masuda S, Okano M, Yamagishi K,Nagao M, Ueda M, Sasaki R. A novel site of erythropoietin production. Oxygen-dependentproduction in cultured rat astrocytes [ J]. J Biol Chem. 1994, 269(30): 19488-19493.