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  

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

作　　者：潘晓明[1] 吴玲玲[1] 陈浩浩[1] 傅晓艳[1] 王文倩 江文娇 张辉 丁明星[1] Pan Xiaoming;Wu Lingling;Chen Haohao;Fu Xiaoyan;Wang Wenqian;Jiang Wenjiao;Zhang Hui;Ding Mingxing(Department of Anatomy,School of Medicine,Jinhua Polytechnic College,Jinhua 321007;Jinhua Sidanmu Stem Cell Biotechnology Limited Company,Jinhua 321007;Jinhua Food and Drug Inspection Institute,Jinhua Center of Laboratory Animals,Jinhua 321000,China)

机构地区：[1]金华职业技术学院医学院解剖学教研室,金华321007 [2]金华市思丹姆干细胞生物科技有限公司,金华321007 [3]金华市食品药品检验检测研究院,金华市实验动物中心,金华321000

出　　处：《解剖学杂志》2020年第1期3-9,共7页Chinese Journal of Anatomy

基　　金：2019年浙江省实验动物科技计划项目（LGD19H090002）;2017年金华市科技研究计划项目（2017-4-048）

摘　　要：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。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 red

关 键 词：人脐带间充质干细胞 脊髓损伤 神经病理性痛 小鼠 

分 类 号：R457.7[医药卫生—治疗学] R651.2[医药卫生—临床医学]