脑室周围白质软化症再髓鞘化的研究进展  

Progress of remylination in periventricular leukomalacia

作　　者：陈鹏慧[1] 

机构地区：[1]第三军医大学神经生物学教研室,重庆400038

出　　处：《遵义医学院学报》2014年第1期20-25,共6页Journal of Zunyi Medical University

基　　金：国家自然科学基金面上项目(NO:81070515);国家级大学生创新创业训练计划项目(NO:201290035009)

摘　　要：脑室周围白质软化症(Periventricular leukomalacia,PVL)是一种与神经发育相关、以大脑损伤为主、并最终导致脑瘫和认知障碍的一种早产儿脱髓鞘疾病。其主要特征为大脑脑室周围白质的损害,其中最重要的靶细胞是成髓鞘前的少突胶质细胞(premyelinating oligodendrocyte,Pre-OLs)。PVL的发病机制主要与缺血缺氧损伤、全身感染和炎症反应、小胶质细胞活化、兴奋性氨基酸、自由基损害和大脑白质Pre-OLs自身的发育易损性相关。在PVL脱髓鞘损伤,中枢神经系统通过一系列髓鞘化相关机制来促进和恢复髓鞘的再生。包括转录因子的改变、转录后miRNA的调节以及各种组蛋白去乙酰化酶的表观遗传学调控作用。其中,鞘磷脂基因调节因子是髓鞘化至关重要的因子,其主要作用是使Pre-OLs向成熟的少突胶质细胞分化,鞘磷脂基因调节因子也受其他转录因子调控。Periventricular leukomalacia （PVL） ,associated with a high risk of neurodevelopmental disability,is the predominant form of brain injury and the leading known cause of cerebral palsy and cognitive deficits in pre- mature infants. The principal feature of PVL involves cerebral white matter and the principal cellular target is premyelinating oligodendrocyte （pre - OLs）. The pathogenesis of PVL relates to hypoxia - ischemia injury, sys- temic infection/inflammation, microglial activation, excitotoxicity, free radical attack and maturation -depend- ent vulnerability of cerebral white matter pre - OLs. After the demyelination injury of PVL, the organism starts a series of cellular events involved in remyelination, which include changes in transcription factor expression within oligodendrocyte precursor cells （OPCs） associated with their activation in response to demyelination, miRNA post - transcriptional regulation of oligodendrocyte differentiation and epigenetic regulation of histone deacetylases （HDACs） in control of OPCs differentiation during remyelination. Myelin gene regulatory factor is a critical tran- scriptional regulator required for myelination, and induces the Pre - OLs to differentiate into mature oligodendro- cytes.

关 键 词：脑室周围白质软化症 少突胶质细胞 鞘磷脂基因调节因子 成髓鞘前少突胶质细胞 髓鞘 

分 类 号：R742.3[医药卫生—神经病学与精神病学]