Nogo髓鞘相关蛋白受体拮抗剂与缺氧缺血性脑损伤新生大鼠神经元再生的关系  

Association of Nogo-A Receptor Antagonist and Neurite Outgrowth in Neonatal Rats with Hypoxic-Ischemic Brain Damage

作　　者：朱薇薇[1] 王丽[1] 邱丽筠[1] 罗焕华[1] 

机构地区：[1]山东大学附属济南市中心医院小儿内科,济南250013

出　　处：《实用儿科临床杂志》2009年第14期1068-1070,共3页Journal of Applied Clinical Pediatrics

基　　金：山东省自然科学基金资助(Z2005C03)

摘　　要：目的探讨Nogo髓鞘相关蛋白(Nogo-A)受体拮抗剂NEP1-40与新生大鼠缺氧缺血性脑损伤(HIBD)后神经再生的关系。方法将64只新生大鼠随机分为8组:6h、24h时段的对照组,HIBD模型组(HIBD组),NEP1-40治疗组(NEP1-40组)及神经节苷脂治疗组(GM-1组),分别依次腹腔注射9g/L盐水0.25mL/kg、9g/L盐水0.25mL/kg、NEP1-4010mg/kg、GM-120mg/kg。用免疫组织化学法观察各组新生大鼠脑组织Nogo-A阳性细胞的表达情况,透射电镜观察其脑组织超微结构的动态变化。应用SPSS13.0软件行单因素方差分析。结果6h、24hHIBD组脑组织Nogo-A阳性细胞表达均显著高于同时段对照组(t=7.63,15.13Pa<0.01);NEP1-40组Nogo-A阳性表达减少,与同时段HIBD组比较有统计学差异(t=4.38,18.0Pa<0.01);GM-1组Nogo-A阳性表达在6h时与HIBD组比较无明显差异(t=0.25P>0.05),在24h时较HIBD组显著降低(t=4.25P<0.01),但6h、24h均高于NEP1-40组(t=15.10,6.70Pa<0.01)。NEP1-40及GM-1治疗后新生大鼠脑组织超微结构得以不同程度恢复。结论Nogo-A在HIBD中表达显著增高,可抑制中枢神经损伤后的再生,NEP1-40能拮抗这一作用,从而促进HIBD后神经的再生。Objective To explore the possible effect of Nogo - A receptor antagonist NEP1 - 40 on neurite outgrowth in neonatal rats with hypoxic - ischemic brain damage（HIBD）. Methods Sixty - four healthy Wistar rats were randomly divided into 8 groups at 2 different time points（6 h,24 h） ：control grnup,HIBD group,NEP1 -40 group and ganglioside group（ GM - 1 group）. Rats of control group and HIBD group were injected with saline （0.25 mL/kg）by intraperitoneal injection, while rats of NEP1 -40 group and GM - 1 group were administrated with 10 mg/（kg · d） NEP1 -40 and 20 mg/（kg · d） GM - 1 on request in each group,respectively. I staining was adopted to detect the Nogo -A -positive cells ,and ultrastructural changes of neuron and axon were observed by transmission electron microscopy. SPSS 13. 0 statistical software was used to run One - Way ANOVA tests on the data presented. Results The Nogo - A - positive cells at 2 time points in rats of HIBD group were significantly higher than those of control group （ t = 7.63,15.13 P, 〈 0.01 ） ; downregulated level of Nngo - A - posi- tive cells was observed in NEP1 -40 group, as had statistical significance from those of HIBD group（ t = 4.38,18.0 Pa 〈 0.01 ） ; Additionally, there was no difference of the expression of Nogo - A - positive cells at time point of 6 h between GM - 1 group and HIBD group （ t = 0.25 P 〉 0. 05） ,while the Nogo - A - positive ceils in GM - 1 group at 24 h was lower than that of HIBD group （ t = 4.25 P 〈 0. 01 ）, but higher than that of NEP1 - 40 group at 6,24 h（t = 15.10,6.70 Pa 〈 0.01 ）. Repair of neurons in damaged brain was gained to some extent after GM - 1 treatment and satisfactory repair of neurons and regrowth of axon was obtained with NEP1 -40 administration through transmission electron micrescopy. Conclusions The expression of Nogo - A up - regulate dramatically following HIBD,which may exert inhibitory effect on neuronal regeneration of the central nervous system of HIBD. NEP1 -40 can antagon

关 键 词：Nogo髓鞘相关蛋白 缺氧缺血 脑 再生 Nogo受体拮抗剂 

分 类 号：R722.1[医药卫生—儿科]