新生期缺氧缺血大鼠脑白质损伤及脑内Fyn、p-ERK和MBP下调

Hypoxic-ischemic white matter injury and down-regulation of Fyn,p-ERK and MBP in neonatal rat brain

目的检测新生大鼠缺氧缺血后脑内酪氨酸蛋白激酶Fyn、p-ERK及髓鞘碱性蛋白(myelin basic protein,MBP)表达的变化,探讨Fyn-ERK通路在缺氧缺血脑白质损伤中的作用。方法新生3日龄SD大鼠24只,随机分为对照组和缺氧缺血(HI)组。缺氧缺血后4周,应用HE染色法观察脑组织病理学改变;应用免疫荧光染色法和Western blot法观察Fyn、p-ERK及MBP在大鼠脑内的定位定量表达变化。结果 HE染色显示缺氧缺血大鼠出现缺氧缺血脑白质损伤病理改变;免疫荧光染色和Western blot检测显示脑内Fyn、p-ERK和MBP水平均明显下调。结论新生期缺氧缺血损伤4周后,可能通过Fyn与p-ERK水平的下调而使MBP减少,进而使少突胶质细胞成熟障碍,引起脑白质损伤。

Objective To understand the role that Fyn-ERK pathway plays in hypoxic-ischemic white matter injury in neonatalrats.Methods3-day-old new born SD rats were randomly divided into control and hypoxic-ischemic groups.The histology of rat braintissues4weeks after operation was examined using HE staining.The distribution and expression level of Fyn,p-ERK and MBP proteinwere detected by immunocytochemistry and western blotting.Results The white matter injury was observed in hypoxic-ischemic rats.The levels of Fyn,p-ERK and MBP protein significantly decreased in the brains of hypoxic-ischemic rats,compared to the controlgroup.Conclusion The results suggest that hypoxia-ischemia may decrease MBP level in neonatal rats through downregulating Fynand p-ERK protein levels,which may lead to oligodendrocyte maturation disorder and white matter injury.