少突胶质前体细胞移植治疗早产儿脑白质损伤大鼠模型

Long-term effect of oligodendrocyte precursor cell transplantation on a rat model of white matter injury in the preterm infant

摘要:

目的 探讨少突胶质前体细胞（OPCs）移植对治疗早产儿脑白质损伤（WMI）模型大鼠的长期作用。方法 将80只3日龄Sprague-Dawley大鼠随机分为假手术组、模型对照组、5 d脑室/白质移植组、9 d脑室/白质移植组、14 d脑室/白质移植组（n=10）；除假手术组外其余各组行右侧颈总动脉离断并缺氧80 min制备早产儿WMI模型；采用孕10~12周人胚胎脑组织制备OPCs。各移植组分别在造模后5 d、9 d和14 d将3×10⁵ OPCs注入右侧脑室/脑白质中，待大鼠60日龄和90日龄时分别对各组行电镜下脑髓鞘评估和神经功能评估。结果 电镜下，大鼠60日龄时各移植组髓鞘损害程度相比模型组略有改善；无论是与同组60日龄大鼠还是与同日龄模型组大鼠比较，90日龄时各移植组的髓鞘均明显增厚，结构破坏更少，其中14 d移植组变化最为明显；但不同移植时间脑室和白质移植组间的髓鞘损害程度未见有明显差异。60及90日龄各移植组大鼠的神经功能缺陷评分（mNSS）均高于假手术组，但均低于模型组（P < 0.05）。结论 OPCs移植可能对治疗早产儿WMI存在长期效应，延迟移植时间可能增强疗效。

Abstract:

Objective To investigate the long-term effect of oligodendrocyte precursor cell (OPC) transplantation on a rat model of white matter injury (WMI) in the preterm infant. Methods A total of 80 Sprague-Dawley rats aged 3 days were randomly divided into sham-operation group, model control group, 5-day ventricular/white matter transplantation group, 9-day ventricular/white matter transplantation group, 14-day ventricular/white matter transplantation group (n=10 each). All groups except the sham-operation group were treated with right common carotid artery ligation and hypoxia for 80 minutes to establish a rat model of WMI in the preterm infant. OPCs were prepared from the human fetal brain tissue (10-12 gestational weeks). At 5, 9, and 14 days after modeling, 3×10⁵ OPCs were injected into the right lateral ventricle or white matter in each transplantation group, and myelin sheath and neurological function were evaluated under an electron microscope at ages of 60 and 90 days. Results Electron microscopy showed that at an age of 60 days, each transplantation group had a slight improvement in myelin sheath injury compared with the model control group; at an age of 90 days, each transplantation group had significantly thickened myelin sheath and reduced structural damage compared with the model control group, and the 14-day transplantation groups had the most significant changes. There were no significant differences in the degree of myelin sheath injury between the ventricular and white matter transplantation groups at different time points. At an age of 60 or 90 days, the transplantation groups had a significantly higher modified neurological severity score (mNSS) than the sham-operation group and a significantly lower mNSS than the model control group (P < 0.05). Conclusions OPC transplantation may have a long-term effect in the treatment of WMI in the preterm infant, and delayed transplantation may enhance its therapeutic effect.