少突胶质细胞髓鞘来源抑制蛋白及其受体的研究进展

Research progress in oligodendrocyte-myelin associated inhibitors and its receptors

目的:成年哺乳动物中枢神经系统损伤后,少突胶质细胞和髓鞘来源的几种抑制蛋白能够显著抑制其再生,通过与共同的Nogo-66受体结合而发挥抑制轴突再生的作用。近来发现Nogo-A及髓鞘相关糖蛋白还有另外的不同于Nogo-66受体途径,为进一步研究中枢神经系统损伤后再生提供了新思路。本文就Nogo-A、髓鞘相关糖蛋白、少突胶质细胞髓鞘糖蛋白及其受体的研究进展作一综述。资料来源:应用计算机检索PUBMED1981-01/2004-05期间的相关文章,检索词为“Nogo-A,MAG,OMgp,NgR”,并限定文章语言种类为English。资料选择:选取实验为各类型中枢神经系统损伤的大鼠模型的相关实验,进行初审,删除明显不符合动物模型实验的研究,然后查找余下的文献全文,进一步判断是否为随机动物模型实验。纳入标准:①随机动物模型试验,无论是否为单盲、双盲或非盲法。②平行对照组为脊髓未受损伤的大鼠动物模型,治疗组为中枢神经系统受损的大鼠模型。排除标准:明显不随机的动物模型试验或非动物模型研究;质量评价主要考察资料的真实性,试验设计是否合理,观测检验过程是否严格,统计学处理是否有说服力;重复研究或Meta分析类文章。资料提炼:共检索到30篇相关文献,排除的6篇文献中,2篇是重复的同一研究,4篇不符合大鼠模型试验。共24篇文献符合纳入标准,其中7篇涉及Nogo-A蛋白,8篇涉及髓鞘相关糖蛋白,5篇涉及少突胶质细胞髓鞘糖蛋白,5篇涉及Nogo-66受体及其他受体。资料综合:Nogo-A包含Nogo-66和amino-Nogo两个功能性结构域,对轴突生长均有抑制作用。髓鞘相关糖蛋白不仅对成年轴突生长具有抑制作用,且可以促进新生神经元轴突生长。少突胶质细胞髓鞘糖蛋白是糖基磷脂酰肌醇锚合蛋白,富含亮氨酸重复片段结构域,参与蛋白间的相互作用,发挥DNA修复、RNA剪接、细胞间黏附及信号转导等功能。结论:成年哺乳动物中枢神经系统受损后,几种主要的抑制蛋白与共受体结合而发挥抑制轴突再生的作用,为进一步研究中枢神经系统损伤后再生做铺垫。

OBJECTIVE： After the injury of adult mammal animal central nerve systems, many factors inhibit the regeneration, among which oligodendrocyte and myelin associated inhibitors are important. They inhibit axon regeneration through combination with common receptor Nogo- 66. Recently, we have also found that there are different receptor approaches with Nogo-A, myelin associated glucoprotein （MAG）, and these have provided new ways for later research of regeneration after central nervous system （CNS） injury. This text is aimed to review the research development of Nogo-A, MAG, oligodendrocyte myelin glycoprotein （OMgp） and its receptors. DATA SOURCES： We searched the PUBMED database for related articles with the key words of ＂Nogo-A, MAG, OMgp, NgR＂ published from January 1981 to May 2004 in English. STUDY SELECTION： The literatures of rat model for CNS injury were selected firstly, and those were not about the study of animal model were deleted, and then the full-texts of the rest ones were searched. Whether these included randomized animal models experiments or not were judged further. Inclusive criteria： ①the randomized experiments of animal models, no matter single blind, double blind or non-blind trials;②the parallel- control groups included un-treated or healthy animal models. Treatment group contained animal models with CNS injury. Exclusive criteria： those were obvlously non-randomized research or non-anlmal model research. Evaluation： the tacticity of the material, the rationality of the experiments, the exactness of the observation and tests, the stringency of the statistics; repetitive research or Meta analysis articles. DATA EXTRACTION： Totally 30 relatod articles were collected. Of the 6 excluded articles, 2 ones were duplicated researches, 4 ones were not rat-models. Totally 24 articles were accorded with the inclusive criteria, of which 7 papers were related to Nogo-A, 8 papers were related to MAG, 5 papers were related to OMgp, 5 papers were related to Nogo-66 receptor and others. DATA SYNTHESIS： Nogo-A included Nogo-66 and amino-Nogo functional structural domains, which had inhibitory effect on axon growth. MAG not only could inhibit adult axon growth, but also promote the growth of new axon. OMgp, a glyeosyl-phosphatidyl inositol anchor protein, was rich in leucine repeated segments, participated in interaction among protein, had the function of DNA repair, RNA splicing, cell adhesion, signal transduetion and so on. CONCLUSION： Various factors inhibit axon regeneration through combination with common receptors in adult mammalian after CNS injury. These have provided basis for later research of regeneration after CNS injury.