Nogo受体及其拮抗剂与神经节苷脂在新生大鼠HIBD中的作用

Effect of NEP1-40 and GM-1 on hypoxic ischemic brain damage in newborn rats

目的观察Nogo-A受体拮抗剂NEP1-40及神经节苷脂对新生大鼠缺血缺氧性脑损伤后神经再生的作用。方法将100只7日龄新生大鼠随机分为10组:在6 h、24 h两个时间段分别设空白对照组,假手术组,缺氧缺血性脑损伤(HIBD)模型组,HIBD后NEP1-40治疗组及神经节苷脂治疗组,用原位杂交的方法观察各组别Nogo-A mRNA的表达情况。结果HIBD组两时段的Nogo-mRNA表达均高于同时段空白组及假手术组,差异有统计学意义;NEP1-40治疗组能抑制HIBD后mRNA的表达,与同时段模型组对比差异有统计学意义;神经节苷脂治疗组mRNA的表达在6h时与HIBD组无明显差异,在24h时较HIBD组低但高于空白组。P值均<0.05。结论Nogo-A mRNA在缺氧缺血性脑损伤后表达显著增高,其编码的Nogo-A可抑制中枢神经损伤后的再生,NEP1-40能拮抗这一作用,从而可能在促进缺氧缺血性脑损伤后神经再生中起到作用。神经节苷脂GM-1在缺氧缺血性脑损伤后也可抑制Nogo-A mRNA的表达,有稳定细胞膜、减轻细胞水肿、促进神经再生的作用。

Objective To investigate the effects of NEP1-40 and GM-1 in newborn rats with hypoxic ischemic brain damage （HIBD）. Methods 100 rats were randomly divided into 10 groups and five groups were treated in different ways at 6 h： the normal control group, the sham-operation group, the HIBD model group, the GM-1 treatment group and the NFP1-40 treatment group, and the other five groups were treated at 24 h. Contents of Nogo-A mRNA in each group were determined by the method of in situ hybridization. Results The expression of Nogo-A mRNA in the HIBD groups was higher than that in the control groups, and was lower in the NEP1-40 groups than in the HIBD groups at both time points. There were no significant differences between the GM-1 group and the HIBD group when they were treated at 6 h. However, the expression of Nogo-A mRNA was lower in the GM-1 group than in the HIBD group but was higher than the normal control group. Conclusion Nogo-A mRNA is sig- nificantly increased in newbom rats with HIBD. Nogo-A encoded by mRNA can inhibit the regeneration of the central nerve after injury, and NEP1-40 could antagonize the function and promotes the regeneration. GM-1 is also able to antagonize the expression of mRNA and stabilizes the cellular membrane, eases cellular edema of the injured nerve and accelerates the regeneration of new nerves.