Nogo-A及其受体拮抗剂在新生大鼠缺氧缺血性脑损伤修复中的作用机制

Mechanism of Nogo-A and its receptor antagoist during repairing of hypoxicia-ischemic brain damage in newborn rats

【目的】探讨Nogo-A及其受体拮抗剂NEP1-40在新生大鼠缺氧缺血性脑损伤修复中的作用。【方法】将64只新生7日龄大鼠按6h、24h两个时段随机分为8组,空白对照组、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),依次分别腹腔注射0.9%氯化钠0.25mL/kg、0.9%氯化钠0.25mL/kg、NEP1-4010mg/kg、GM-120mg/kg。原位杂交法观察各组Nogo-A的表达情况,透射电镜观测脑组织超微结构的动态变化。【结果】Nogo-A阳性细胞的表达:对照组两时段细胞数均随着时间的延长而略增加,两时段比较无统计学意义(P均>0.05)。HIBD组两时段均高于同时段对照组,NEP1-40组表达明显减少,与同时段HIBD组对比有显著统计学意义;GM-1组较HIBD组低,但高于NEP1-40组。NEP1-40及GM-1治疗后脑组织超微结构得以不同程度恢复(P均<0.05)。【结论】Nogo-A可抑制中枢神经损伤后的再生,NEP1-40能拮抗这一作用并促进神经元再生,GM-1在HIBD神经损伤修复中亦能促进再生。

[Objective] To investigate the function of Nogo-A on hypoxicia-ischemic brain damage（HlBD） and the effects of antagoist during repairing of HIBD in newborn rats. [Methods] 64 healthy Wistar rats were randomly divided into 8 groups at 2 different time points（6 h, 24 h） ：the control group, HIBD group, NEP1-40 group and ganglioside group （GM-lgroup）. Rats of the control group and HIBD group were injected with saline （0.25 mL/kg）by intraperitoneal injection, while rats of NEP1-40 group were administrated with NEP1-40 10 mg/（kg.d） and GM-1 group with GM-1 20 mg/ （kg . d） on request in each group,respectively. [Results] Contents of Nogo-A in each group were determined by the method of in situ hybridization and the pathological changes were observed by transmission electronmicroscopy. The expression of Nogo-A in control groups increased along with the time and there was no significance between two time points. The expression of Nogo-A at two time points in HIBD groups were significantly higher than that of the control groups of the corresponding time; downregulated level of Nogo-A expression was observed at NEP1-40 groups, which had statistical significance from that of HIBD. There was no difference of the expression of Nogo-A at 6h between GM-1 and HIBD groups, while the GM-1 groups were lower than that of HIBD at 24 h, but these were all higher than NEP1-40 groups. Satisfactory repair of neurons and regrowth of axon was obtained with NEP1-40 administration in damaged brain and it was gained to some extent after GM-1 treatment and P value was less than 0.05. [Conclusions] Nogo-A can inhibit the regeneration of central nerve after being injured, while NEP1-40 can antagonize the function and accelerate the regeneration of new nerve simultaneously. GM-1 is also able to accelerate the regeneration of new nerve.