脑室注射Nogo-A抗体对HIBD新生大鼠脑组织神经细胞再生的影响  

Effect of ventricle injection of Nogo-A antibody on neuronal regeneration following hypoxic-ischemic brain damage in the neonatal rat

作　　者：周晓光[1] 刘仁红 熊爱华[3] 

机构地区：[1]广州医学院第二附属医院新生儿科,广东广州510260 [2]深圳市宝安区沙井人民医院儿科,广东深圳518104 [3]暨南大学药学院实验中心,广东广州510632

出　　处：《中国当代儿科杂志》2007年第4期301-304,共4页Chinese Journal of Contemporary Pediatrics

基　　金：广东省医学科学技术研究基金资助项目(A2004305)

摘　　要：目的Nogo-A对中枢神经轴突的生长具有很强的抑制作用,而Nogo-A特异性抗体IN-1能中和这种抑制性蛋白,从而促进损伤轴突的再生。该文旨在探讨脑室注射Nogo-A抗体(IN-1)对缺氧缺血性脑损伤(HIBD)新生大鼠脑组织神经细胞再生的影响。方法建立新生大鼠HIBD模型,随机分为IN-1组和人工脑脊液组,每组20只,前者脑室注射IN-110μL,后者脑室注射人工脑脊液10μL,另外选择20只新生大鼠为假手术组,只施行颈部手术分离颈总动脉,但不结扎,不做缺氧缺血处理。应用免疫组织化学ABC法结合图像分析研究其脑组织Nogo-A及GAP-43蛋白表达水平。结果IN-1组新生鼠脑组织Nogo-A蛋白表达弱于人工脑脊液组,前者Nogo-A免疫组化阳性细胞数(28.61±1.70)也较后者(39.52±1.40)明显减少,两者比较差异具有显著性(P<0.01);IN-1组Nogo-A免疫组化阳性细胞数明显少于假手术组(32.78±1.87),两者比较差异具有显著性(P<0.01);而人工脑脊液组(39.52±1.40)明显多于假手术组(P<0.01)。IN-1组GAP-43蛋白的表达(31.14±1.88)强于人工脑脊液组(27.73±1.43),两组GAP-43免疫组化阳性细胞数比较差异具有显著性(P<0.01);IN-1组及人工脑脊液组GAP-43免疫组化阳性细胞数明显少于假手术组(33.64±1.24),差异均有显著性(P<0.01)。结论Nogo-A抗体可导致HIBD新生大鼠脑组织Nogo-A蛋白表达明显减少,对神经细胞再生的抑制作用减弱。而脑组织神经细胞GAP-43表达增强,提示神经细胞再生作用增强。Objective Nogo-A antibody IN-1 can neutralize Nogo-A, a neurite growth inhibitory protein, promoting axonal regeneration following lesions of the central nervous system （CNS） in adult rats. This study aimed to examine the effect of ventricle injection of Nogo-A antibody on neuronal regeneration in neonatal rats following hypoxic-ischemic brain damage （HIBD）. Methods A model of neonatal HIBD was prepared by the ligation of the left common carotid artery, followed by 8% hypoxia exposure. Forty HIBD rats were randomly given a ventricle injection of 10 μL Nogo-A antibody IN- 1 （IN-1 group） or 10 μL artificial cerebrospinal fluid （artificial CSF group） （n--20 each）. Another 20 neonatal rats were sham-operated, without hypoxia-ischemia, and were used as the controls. The levels of Nogo-A and GAP-43 protein in the brain were measured by immunohistochemistry. Results The number of immunohistory positive cells of Nogo-A in the brain in the IN-1 group （28.61 ± 1.70） was obviously less than that in the artificial CSF （39.52 ± 1.40） and the shamoperated groups （32.78 ±1.87 ） （both P 〈 0.01 ）. There were significant differences in the Nogo-A protein expression between the artificial CSF and the sham-operated groups （ P 〈 0.01 ）. The GAP-43 protein expression in the IN-1 group （ 31.14 ± 1.88） was noticeably higher than that in the artificial CSF group （27.73 ± 1.43 ） （ P 〈 0.01 ）. Both the IN-1 and the artificial CSF groups showed lower GAP-43 protein levels than the sham-operated groups （ 33.64 ±1.24） （ both P 〈 0.01 ）. Condusions Nogo-A antibody can reduce the expression of Nogo-A protein in the brain and thus promote neuronal regeneration in neonatal rats following HIBD. An increased GAP-43 protein expression in the brain after Nogo-A antibody administration shows an enhanced neuronal regeneration in the neonatal rats following HIBD.

关 键 词：缺氧缺血性脑损伤 NOGO-A GAP-43 新生大鼠 

分 类 号：R722.1[医药卫生—儿科]