BMP-4在视网膜与视神经中的分布及对少突胶质前体细胞分化的影响  

The distribution of BMP-4 in rat retina and optic nerve and its effects on the differentiation of oligodendrocyte precursors

作　　者：刘培培[1] 陈园园[1] 郑华[1] 李艳[1] 佘振珏[1] 肖虹蕾[1] 周国民[1] 

机构地区：[1]复旦大学上海医学院解剖与组织胚胎学系,上海200032

出　　处：《神经解剖学杂志》2010年第5期459-464,共6页Chinese Journal of Neuroanatomy

基　　金：国家自然科学基金(30971536)

摘　　要：目的:研究骨形态发生蛋白4(bone morphogenetic protein4,BMP-4)在视网膜与视神经上的表达情况及其对少突胶质前体细胞(oligodendrocyte precursor cells,OPCs)分化的影响,进一步探讨视神经乳头处无髓鞘形成的原因。方法:取生后7d SD大鼠视神经,用免疫组织化学方法研究BMP-4的表达情况。采用恒温振荡法和差速贴壁法分离纯化新生SD大鼠OPCs。用BMP-4诱导OPCs分化,通过免疫细胞化学方法研究OPCs的分化方向。通过Western Blot方法研究BMP-4浓度与OPCs细胞体系内Olig2蛋白表达水平之间的相互关系。结果:(1)在发育过程中,BMP-4仅选择性表达在视神经乳头处;(2)成功纯化的OPCs在PDGF和bFGF撤除后自发分化为少突胶质细胞;(3)OPCs经BMP-4诱导后向II型星形胶质细胞分化;(4)OPCs内Olig2蛋白的表达量随着BMP-4浓度的逐渐增高而逐渐降低。结论:在视神经乳头表达的BMP-4蛋白有可能作用于迁移至此处的OPCs,通过激活相关信号途径以下调OPCs内Olig2蛋白的表达水平,抑制OPCs向少突胶质细胞方向分化,从而抑制视神经乳头髓鞘形成。Objective：To research the expression of BMP-4 in retina and optic nerve and its effects to the differentiation of oligodendrocyte precursor cells（OPCs）,to further explain the cause of amyelination in optic nerve head.Methods：Frozen sections of longitudinal P7 optic nerve and retina were labeled with antibodies to BMP-4 to define in more details the spatial and temporal distribution of BMP-4.The modified mixed glial culture and different-attachment method were used to harvest OPCs from the P0-P1 postnatal SD rats.And immunocytochemical stain was used to observe the induction of BMP-4 to the differentiation of OPCs.Also,the relationship between BMP-4 and Olig2 were detected by western Blot.Results：（1）Strong expression of BMP-4 was detected in the optic nerve head.（2）The cultured OPCs automatically differentiated into mature oligodendrocytes after PDGF and bFGF withdrawn.（3）Exposed to high concentration of BMP-4 could promote the differentiation of type 2 astrocytes.（4）With gradually increased concentration of BMP-4,the expression of Olig2 decreased.Conclusion：The expression of BMP-4 in the optic nerve head inhibit the differentiation into oligodendrocytes of OPCs that succeed in migrating through the lamina cribrosa at the optic nerve/retina junction thereby ensuring a lack of retinal myelination.This effect could be completed by activating some related signal pathway and downregulating the expression olig2.

关 键 词：BMP-4 少突胶质前体细胞 OLIG2 视神经乳头 无髓鞘形成 

分 类 号：R322.9[医药卫生—人体解剖和组织胚胎学]