[1]张梅梅△,闫方方,蒋 超,等.重组人促红细胞生成素对短暂性缺氧新生大鼠的神经保护作用[J].郑州大学学报(医学版),2016,(03):382-385.
 ZHANG Meimei,YAN Fangfang,JIANG Chao,et al.Neuroprotective effect of recombinant human erythropoietin for transient cerebral hypoxia neonatal rats[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2016,(03):382-385.
点击复制

重组人促红细胞生成素对短暂性缺氧新生大鼠的神经保护作用()
分享到:

《郑州大学学报(医学版)》[ISSN:1671-6825/CN:41-1340/R]

卷:
期数:
2016年03期
页码:
382-385
栏目:
应用研究
出版日期:
2016-05-20

文章信息/Info

Title:
Neuroprotective effect of recombinant human erythropoietin for transient cerebral hypoxia neonatal rats
作者:
张梅梅闫方方蒋 超孟 颜
郑州大学第五附属医院儿童康复医学科 郑州 450052
Author(s):
ZHANG MeimeiYAN FangfangJIANG ChaoMENG Yan
Department of Pediatric Neurology,the Fifth Affiliated Hospital,Zhengzhou University,Zhengzhou 450052
关键词:
促红细胞生成素 缺氧缺血性脑病 新生大鼠 神经保护作用
Keywords:
erythropoietin hypoxic-ischemia encephalopathy neonatal rat neuroprotective effect
分类号:
R722
摘要:
目的:探讨重组人促红细胞生成素(rhEPO)对新生大鼠缺氧缺血性脑病(HIE)的神经保护作用。方法:将7日龄雄性SD大鼠随机分为对照组、单纯缺氧组和治疗组。对照组不做缺氧处理,治疗组先建立短暂性脑缺氧大鼠模型,后经腹腔注射法给予rhEPO 治疗,对照组和单纯缺氧组于相同时间点腹腔注射等量生理盐水。采用干-湿重法测量脑组织含水量,尼氏染色观察海马CA1区神经元形态学变化,Western bolt检测海马组织中凋亡相关蛋白cleaved-Caspase-3、Bcl-2、Bax的表达情况。Morris水迷宫检测大鼠的神经行为学变化。结果:与对照组相比,单纯缺氧组大鼠脑组织含水量增加,海马CA1区退行变性神经元数目增多(P<0.001),细胞核固缩、深染明显; cleaved-Caspase-3、Bcl-2及Bax表达增加(P<0.001)。治疗组与单纯缺氧组相比,脑组织含水量及海马CA1区变性神经元数目明显减少,cleaved-Caspase-3、Bax表达减少而Bcl-2表达增加(P<0.05)。单纯缺氧组大鼠的学习记忆能力较对照组明显下降,而治疗组的学习记忆能力较单纯缺氧组有显著改善(P<0.001)。结论:rhEPO对HIE新生大鼠具有神经保护作用,能够减轻急性期脑水肿及海马神经元损伤,改善大鼠学习记忆能力。
Abstract:
Aim: To explore the neuroprotective effect of recombinant human erythropoietin(rhEPO)for hypoxic-ischemic encephalopathy(HIE)in neonatal rats.Methods: Seven-day-old SD neonatal rats were randomly allocated into three groups: control group, anoxia group and rhEPO treatment group. The control group did not undergo anoxia. After the establishment of anoxia model, the rhEPO treatment group received rhEPO by intraperitoneal injection. Neonatal rats in control group and anoxia group received the treatment with the same volume of normal saline at the same time point. Brain water content(BWC)was estimated by dry-wet method; morphological changes in neurons of hippocampus CA1 area were observed by Nissl staining; apoptosis-related proteins such as cleaved-Caspase-3, Bcl-2 and Bax were measured by Western bolt. Neurological behavior was assessed by Morris water maze test(MWM).Results: Compared with control group, the BWC as well as the number of denatured neurons of hippocampus CA1 area in anoxia group was significantly increased(P<0.001); the nucleus pycnosis and hyperchromasia were evidently seen. In addition, the expressions of cleaved-Caspase-3, Bcl-2 and Bax in anoxia group were significantly increased compared with those of control group(P<0.001). Compared with anoxia group, the BWC, the number of denatured neurons of hippocampus CA1 area and expressions of cleaved-Caspase-3 and Bax in rhEPO treatment group were significantly decreased, while the expression of Bcl-2 was significantly increased(P<0.05). The ability of learning and memory in anoxia group was significantly decreased compared with control group, while the ability of learning and memory in rhEPO treatment group was significantly improved compared with anoxia group(P<0.001).Conclusion: RhEPO has neuroprotective effect by reducing acute brain edema, alleviating injury of neurons in hippocampus and improving the neurological behavior of neonatal rats with HIE.

参考文献/References:

[1] MARTINEZ-BIARGE M,DIEZ-SEBASTIAN J,WUSTHOFF CJ,et al.Antepartum and intrapartum factors preceding neonatal hypoxic-ischemic encephalopathy[J].Pediatrics,2013,132(4):e952
[2] ZUBCEVIC S,HELJIC S,CATIBUSIC F,et al.Neurodevelopmental follow up after therapeutic hypothermia for perinatal asphyxia[J].Med Arch,2015,69(6):362
[3] RANGARAJAN V,JUUL SE.Erythropoietin: emerging role of erythropoietin in neonatal neuroprotection[J].Pediatr Neurol,2014,51(4):481
[4] SAMAIYA PK,KRISHNAMURTHY S.Characterization of mitochondrial bioenergetics in neonatal anoxic model of rats[J].J Bioenerg Biomembr,2015,47(3):217
[5] 何远宏,李魁,王建平,等.骨髓单个核细胞移植对脑出血大鼠的影响[J].郑州大学学报(医学版),2014,02(2):264
[6] TORUN YA,OZDEMIR MA,ULGER HA,et al.Erythropoietin improves brain development in short-term hypoxia in rat embryo cultures[J].Brain Dev,2014,36(10):864
[7] JUUL SE,FERRIERO DM.Pharmacologic neuroprotective strategies in neonatal brain injury[J].Clin Perinatol,2014,41(1):119
[8] WANG L,DI L,NOGUCHI CT.Erythropoietin, a novel versatile player regulating energy metabolism beyond the erythroid system[J].Int J Biol Sci,2014,10(8):921
[9] CASTAÑEDA-ARELLANO R,FERIA-VELASCO AI,RIVERA-CERVANTES MC.Activity increase in EpoR and Epo expression by intranasal recombinant human erythropoietin(rhEpo)administration in ischemic hippocampi of adult rats[J].Neurosci Lett,2014,583:16
[10]WANG L,WANG X,SU H,et al.Recombinant human erythropoietin improves the neurofunctional recovery of rats following traumatic brain injury via an increase in circulating endothelial progenitor cells[J].Transl Stroke Res,2015,6(1):50
[11]徐发林,郭佳佳,王彩红,等.不同时机应用促红细胞生成素对感染所致新生大鼠脑损伤的保护作用[J].中华实用儿科临床杂志,2014,29(17):1325
[12]HRALOVÁ M,PLAÑANSKÁ E,ANGEROVÁ Y,et al.Effects of a single dose of erythropoietin on motor function and cognition after focal brain ischemia in adult rats[J].Prague Med Rep,2014,115(1/2):5
[13]WU N,LI W,SHU W,et al.Protective effect of picroside Ⅱ on myocardial ischemia reperfusion injury in rats[J].Drug Des Devel Ther,2014,8:545
[14]WEI P,ZHIYU C,XU T,et al.Antitumor effect and apoptosis induction of Alocasia cucullata(Lour.)G. Don in human gastric cancer cells in vitro and in vivo[J].BMC Complement Altern Med,2015,15:33

相似文献/References:

[1]朱红灿)△,卢欣),赵鹏),等.促红细胞生成素对体外培养的SD大鼠多巴胺能神经元细胞活力的影响*[J].郑州大学学报(医学版),2009,(06):1185.
 ZHU Hongcan),LU Xin),ZHAO Peng),et al.Effects of erythropoietin on viability of dopaminergic neurons of SD rats in vitro[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2009,(03):1185.
[2]文建国,冯锦锦.促红细胞生成素的研究进展和临床应用[J].郑州大学学报(医学版),2015,(06):733.

备注/Memo

备注/Memo:
△女,1960年9月生,本科,主任医师,研究方向:小儿神经病学,E-mail:mmzhang@zzu.edu.cn
更新日期/Last Update: 2016-05-20