促红细胞生成素干预缺氧缺血性脑损伤新生鼠神经干细胞巢蛋白的表达(英文)

Effects of erythropoietin on nestin expression in neural stem cells of neonatal rats with hypoxia-ischemia brain damage

背景:巢蛋白是一种存在于神经干细胞的特异性抗原,在神经系统发生病变或损伤引起再生时广泛表达,因此巢蛋白表达常用作判定神经系统发生病变或损伤后能否促进神经再生的一种手段。目的:从神经再生和神经干细胞激活的角度,探讨外源性促红细胞生成素对新生鼠缺氧缺血性脑损伤后神经干细胞巢蛋白表达的影响。方法:结扎大鼠右侧颈总动脉和8%低氧暴露2h制备新生大鼠缺氧缺血性脑损伤模型。对照组仅游离右侧颈总动脉,不予结扎和缺氧处理。干预组大鼠缺氧缺血后立即腹腔注射重组人促红细胞生成素5000IU/kg,1次/d,连用3d。缺氧缺血性脑损伤组大鼠缺氧缺血后连续腹腔注射等量生理盐水溶液3d。每组随机取8只分别于术后4,7,14d处死。应用免疫组化方法和计算机图像分析技术检测不同时点海马齿状回巢蛋白标记阳性细胞的变化。结果与结论:各时点缺氧缺血性脑损伤组巢蛋白阳性细胞数较对照组增加(P<0.05);各时点干预组巢蛋白阳性细胞较对照组和缺氧缺血性脑损伤组均增加(P<0.05)。3组大鼠海马齿状回区巢蛋白阳性细胞数均于术后7d达高峰。结果提示早期给予重组人促红细胞生成素可促使新生鼠缺氧缺血性脑损伤后海马齿状回区巢蛋白表达增加,促进神经干细胞的增殖再生,在缺氧缺血性脑损伤后神经再生、修复中发挥一定的保护作用。

BACKGROUND：Nestin is a specific antigen of neural stem cells which widely expressed in lesion of nervous system and brain regeneration.Thus, nestin expression is commonly used to assess whether lesion or damage of the nervous system can promote neural regeneration.OBJECTIVE：To investigate the effects of erythropoietin （Epo） on nestin expression in neural stem cells after hypoxia-ischemia brain damage （HIBD） in neonatal rats from the angles of neural regeneration and activation of neural stem cells.METHODS：HIBD model was established by ligation of the right common carotid artery along with 2-hour 8% hypoxia exposure in neonatal rats.The control group was not subjected to hypoxia-ischemia, and the right common carotid artery was dissociated.The treatment group received an intraperitoneal injection of recombinant human erythropoietin （rh-Epo, 5 000 IU/kg） once a day for three days after hypoxia/ischemia, while the two other groups intraperitoneally received normal saline at the same time.In each group, rats were randomly executed immediately, at 4, 7, 14 days after operation （n = 8）.The nestin expression in hippocampal dentate gyrus region was examined by immunohistochemical staining and image quantitative analysis respectively.RESULTS AND CONCLUSION：The number of nestin-positive cells was significantly increased in HIBD group compared to control group at all time points （P0.05）, and it was also significantly increased in treatment group than the other two groups at all time points （P0.05）.The numbers of nestin-positive cells in hippocampal dentate gyrus region were significantly increased, and peaked on day 7 after operation in the three groups.The results showed that exogenous rh-Epo could enhance the expression of nestin in hippocampal dentate gyrus region of neonatal rats with HIBD, and promote the proliferation of neural stem cells.rh-Epo plays an important role in the regeneration and repair of neurocytes damaged by hypoxia-ischemia.