脐血间充质干细胞移植修复缺氧缺血损伤新生大鼠的脑功能

背景：课题计划从神经细胞替代、促进内源性神经干细胞增殖和分化、保护神经元、促进突触重建以及减轻脑白质损伤等方面来探讨脐血间充质干细胞系统移植对新生大鼠缺氧缺血脑损伤后神经功能的修复作用及其机制。目的：观察脐血间充质干细胞由静脉途径移植透过血脑屏障进入脑组织内，对新生大鼠缺氧缺血性脑损伤后脑功能修复的影响。方法：7 d龄SD新生鼠分为3组：假手术组仅分离出左侧颈总动脉而不结扎；缺氧缺血脑损伤组制备缺氧缺血脑损伤模型；细胞移植组在缺氧缺血性脑损伤后第8天尾静脉移植人脐血间充质干细胞，前两组尾静脉注射等量的生理盐水。结果与结论：免疫荧光观察显示移植后5周脐血间充质干细胞迁移到海马，Nissl染色结果显示脐血间充质干细胞移植后，左侧海马DG区锥体细胞尼氏小体明显增加，提示间充质干细胞移植后可分化为神经元。行为学测试结果显示：与假手术组相比，缺氧缺血脑损伤组在T迷宫实验中，自发改变率下降，在放射形迷宫中觅水时间延长，错误次数及重复次数明显增加(P < 0.05)；脐血间充质干细胞静脉移植5周后，上述行为学指标均显著改善(P < 0.05)。提示脐血间充质干细胞静脉移植治疗明显改善和提高了缺氧缺血脑损伤大鼠远期的学习记忆和空间辨别能力。

Effects of intravenous transplantation of human umbilical blood mesenchymal stem cells on the improvement of brain function after hypoxic-ischemic brain damage in neonatal rats

BACKGROUND:We have explored the effect and the mechanism of human umbilical blood mesenchymal stem cells transplantation in repairing neural function after hypoxic-ischemic brain damage in neonatal rats from many aspects, such as the nerve cells replacement, promoting the proliferation and differentiation of endogenous neural stem cells, protecting the neurons, promoting the synaptic reconstruction and reducing the white matter damage.OBJECTIVE:To transplant human umbilical blood mesenchymal stem cells via the vein across the blood-brain barrier and then into the brain tissue, to study the effects of intravenous transplantation of human umbilical blood mesenchymal stem cells in repairing the brain function after hypoxic-ischemic brain damage in neonatal rats.METHODS:The 7 days Sprague-Dawley neonatal rats were divided into three groups: sham-operation group, hypoxic-ischemic brain damage group and transplantation group. In the sham-operation group, the left common carotid artery was isolated without ligation; rats in the hypoxic-ischemic brain damage group were used to establish the hypoxic-ischemic brain damage model; in the transplantation group, the human umbilical blood mesenchymal stem cells were transplanted via tail vein at 8 days after hypoxic-ischemic brain damage, and the rats in the sham-operation group and hypoxic-ischemic brain damage group received intravenous injection of normal saline in the same dose.RESULTS AND CONCLUSION:Immunofluorescence observations showed that the human umbilical blood mesenchymal stem cells migrated to the hippocampus at 5 weeks after transplantation. Nissl staining showed the Nissl bodies of pyramidal cells in left hippocampal dentate gyrus area was increased significantly after transplantation, it indicated that the mesenchyamal stem cells could differentiate into neurons after transplantation. Behavioral test results showed that when compared with the sham-operation group, rats in the hypoxic-ischemic brain damage group had a reduced spontaneous alternation rate in T-maze acquisition tests, the rats took more time in finding the three arms baited with water and had an increased number of working and reference memory errors in radial maze acquisition tests (P < 0.05); at 5 weeks after umbilical blood mesenchymal stem cells transplantation, the indicators above were improved (P < 0.05). Intravenous transplantation of human umbilical blood mesenchymal stem cells can improve and enhance the long-term learning and memory and spatial discrimination ability of hypoxic-ischemic brain damage rats.