脐带间充质干细胞移植对脊髓损伤小鼠运动功能的修复和镇痛作用

目的：探讨人脐带间充质干细胞（ hUC-MSCs）移植缓解脊髓损伤神经病理性痛，并促进功能恢复的效果及 其与脊髓损伤小鼠胶质细胞活化及炎症因子水平的调控关系。方法：建立ICR 小鼠脊髓损伤模型，同时构建慢病毒 载体介导绿色荧光蛋白（ GFP）标记体外培养的 hUC-MSCs ；将模型小鼠分为模型组和治疗组，治疗组于脊髓损 伤1 周后采用局部注射 hUC-MSCs 移植到脊髓中，每周进行运动功能（ BBB）评分及机械性痛觉过敏检测，持续8 周后行组织学评价与炎症因子检测。结果：治疗组脊髓组织中 GFP 荧光有表达。BBB检测结果显示，治疗组和模 型组小鼠随时间延长运动功能均逐渐恢复，其中治疗组运动功能恢复速度要显著快于模型组；机械触诱发痛检测显 示，小鼠脊髓损伤后痛阈值降低，随着时间延长痛阈值逐渐升高。同一个时间点治疗组的痛阈值显著高于模型组。 与模型组相比，治疗组小鼠脊髓组织的白细胞介素-6（ IL-6）、肿瘤坏死因子-α（ TNF-α）表达下降，胶质细胞源 性神经营养因子（ GDNF）表达升高，同时脊髓组织巨噬细胞激活抗原1（ ED1/CD68） 荧光表达显著降低。结论： 脊髓损伤小鼠中hUC-MSCs 移植可能通过降低炎症因子 IL-6 和TNF-α 的分泌，提高 GDNF 的表达水平来促进受损 脊髓组织的修复，并发挥镇痛效应。

Effect of umbilical cord mesenchymal stem cell transplantation on motor function repair and neuropathic pain in mice with spinal cord injury

Objective To explore the effects of transplantion of human umbilical cord mesenchymal stem cells （ hUCMSCs） on alleviating the neuropathic pain from spinal cord injury （ SCI） and promoting functional recovery， and the mechanism of activation of glial cells and regulation of inflammatory factors in SCI mice. Methods SCI models of ICR mice were established by using a spinal cord injury compression model， and lentiviral vector-mediated green fluorescent protein （ GFP）-labeled hUC-MSCs were constructed ； the model mice were divided into treatment group and model group. hUC-MSCs were transplanted into the spinal cords by local injection one week after inducing SCI in the treatment group. Behavioral tests were performed weekly for 8 weeks， which included Basso Beattie Bresnahan （ BBB） scoring of motor function and mechanical hyperalgesia. Histological evaluation and inflammatory factor detection were also conducted. Results GFP fluorescence expression in the spinal cord tissue of the treatment group indicated that the hUC-MSCs carrying the GFP fluorophores were successfully injected and had proliferated in the injured spinal cords. The results of BBB scoring showed that the motor function gradually recovered over time in both groups. The recovery of motor function in the treatment group was significantly faster than that in the model group. Mechanical allodynia test showed that the pain threshold decreased after spinal cord injury in mice. The pain threshold gradually increased over time. For the same time point， the pain threshold of the treatment group was significantly higher than that of the model group. Compared with the model group， the expression of interleukin 6（ IL-6）， tumor necrosis factor-α（ TNF-α） decreased and glial cell-derived neurotrophic factor （ GDNF） in the spinal cord tissue increased， and the fluorescent expression of ED1（CD68） in the spinal cord tissue decreased significantly in the treatment group. This indicated that injury of the spinal cord activated ED1/ CD68 inflammatory macrophages/microglia， and their activation levels were reduced after transplantation of hUC-MSCs. Conclusion It is speculated that hUC-MSCs can enhance the repair of injured spinal cord tissue and exert an analgesic effect by reducing the secretion of inflammatory factors IL-6 and TNF-α and up-regulating the expression level of GDNF.