脑白质损伤模型中Lingo-1的动态变化

Dynamic expression of Lingo-1 in a model of white matter injury

背景:Lingo-1在少突胶质细胞分化和髓鞘形成过程中发挥了重要的负调控作用,其与脑白质损伤可能密切相关,但目前关于脑白质损伤后Lingo-1动态变化的研究,国内尚未见系统报道。目的:观察Lingo-1在脑白质损伤模型不同时间窗的动态表达变化情况。方法:将78只3 d龄SD大鼠随机等分为假手术组和模型组,模型组采用单侧结扎右颈总动脉联合缺氧方法建立脑白质损伤模型,假手术组仅分离右颈总动脉,不作结扎缺氧处理。结果与结论:造模7 d后苏木精-伊红染色以及免疫荧光髓鞘碱性蛋白染色证实模型大鼠白质损伤区呈现选择性白质损伤,提示造模成功。荧光定量q PCR及Western blot结果显示,造模1 d后Lingo-1mRNA及蛋白表达水平即开始明显增高,7 d时达到峰值,此后逐渐降低,至28 d时已基本接近假手术组水平。提示Lingo-1蛋白与脑白质损伤髓鞘损伤密切相关。

BACKGROUND： Lingo-1 has been identified as a negative regulator of oligodendrocyte differentiation and myelination, which may be closely related to the white matter damage, but there is no systematic report on the dynamic changes of Lingo-1 after white matter damage. OBJECTIVE： To explore the dynamic expression of Lingo-1 at different time points after white matter injury in newborn rats. METHODS： Seventy-eight Sprague-Dawley rats aged 3 days old were equally and randomly divided into sham operation group and model group. In the model group, models of white matter injury were established by unilateral ligation of the right common carotid artery combined with hypoxia. In the sham operation group, the right common carotid artery was isolated only, without ligation or hypoxia. RESULTS AND CONCLUSION： At 7 days after model induction, hematoxylin-eosin staining and immunohistochemical staining for myelin basic protein showed that a selective white matter injury was seen at the injury site of a rat model, suggesting successful model establishment. Fluorescent quantitative PCR and western blot assay results demonstrated that the expression levels of Lingo-1 mRNA and protein were significantly up-regulated at 1 day and reached a peak at 7 days post-surgery. After 7 days, above expression was gradually decreased and the up-regulation of Lingo-1 protein lasted to the 28 days post-surgery compared to the sham operation group. These results show that Lingo-1 protein was closely related to the brain white matter injury.