人少突胶质前体细胞移植对脑白质损伤大鼠的保护作用

Protective effect of transplantation of human oligodendrocyte precursor cells in a rat model of white matter injury

摘要:

目的 探究移植人少突胶质前体细胞（hOPCs）治疗早产儿脑白质损伤（WMI）的疗效。方法 将新生大鼠随机分为假手术组、模型组和移植组（n=10）；模型组和移植组大鼠在3日龄时行右侧颈总动脉离断后缺氧2 h，制备WMI模型；从自然流产的11周人类胎儿脑中分离培养hOPCs，将hOPCs移植到WMI模型大鼠中。移植后3个月通过水迷宫实验评估大鼠神经功能，电镜观察大鼠髓鞘厚度和增生情况。结果 在Morris水迷宫定位航行实验中，模型组的逃避潜伏期比假手术组增加；与模型组相比，移植组的逃避潜伏期缩短（P < 0.05）。hOPCs移植在一定程度上减轻了90日龄WMI模型大鼠的认知功能障碍。电镜图像显示，移植hOPCs促进了WMI模型大鼠的大脑髓鞘再生。与假手术组相比，模型组的g-ratio（轴突总直径/纤维总直径）增加，提示髓鞘厚度减小；与模型组相比，移植组的g-ratio降低，提示髓鞘厚度增加（P < 0.05）。结论 鞘内移植hOPCs可以减轻WMI模型大鼠的神经损害并促进髓鞘再生。

Abstract:

Objective To study the effect of human oligodendrocyte precursor cell(hOPC) transplantation in the treatment of white matter injury(WMI). Methods Neonatal rats were randomly divided into a sham-operation group, a model group, and a transplantation group(n=10 each). At the age of 3 days, the rats in the model group and the transplantation group were treated with right common carotid artery ligation, followed by hypoxia for 2 hours, to prepare a rat model of WMI. hOPCs were isolated from a spontaneously aborted human fetal brain at week 11 of gestation, and then hOPCs were cultured and transplanted into the rats with WMI. At 3 months after transplantation, the water maze test was performed to evaluate neurological function, and an electron microscope was used to observe myelin sheath thickness and proliferation. Results The place navigation test using the Morris water maze showed that the model group had a significantly longer escape latency than the sham-operation group, and compared with the model group, the transplantation group had a significant reduction in escape latency(P<0.05). To a certain degree, hOPC transplantation alleviated cognitive impairment in rats with WMI at the age of 90 days. The electron microscope images showed that hOPC transplantation promoted remyelination in the brain of WMI rats. Compared with the sham-operation group, the model group had a significant increase in the g-ratio(total axon diameter/total fiber diameter). Compared with the model group, the transplantation group had a significant reduction in the g-ratio(P<0.05). Conclusions Intrathecal hOPC transplantation may alleviate neurological injury and promote remyelination in a rat model of WMI.