摘要
目的:探究人脐带间充质干细胞(hUC-MSC)移植对未成熟小鼠脑白质损伤的影响。方法:5日龄C57BL/6J小鼠随机分为4组,每组27只。正常对照组不做任何处理,假手术组不切断颈总动脉,模型组和MSC移植组通过切断颈总动脉诱导脑白质损伤模型,MSC移植组造模后侧脑室注射5×10~5个hUC-MSC,模型组给予等体积PBS。术后第7天,每组随机抽取7只,采用核磁共振评估脑梗死情况,之后采用免疫组织化学染色检测小鼠脑组织微管相关蛋白2(MAP-2)、髓鞘碱性蛋白(MBP)的表达,采用免疫荧光染色检测小鼠脑组织神经元、星形胶质细胞、小胶质细胞;术后第24天起,剩余20只小鼠开始通过新物体识别、Y迷宫实验、转棒疲劳实验、CatWalk步态分析进行神经行为学分析;术后第120天,每组取7只,采用DTI评估海马区脑白质发育情况,计算各向异性分数(FA)。结果:与模型组相比,MSC移植组脑梗死体积、白质及灰质损失体积比降低(P<0.05)。与模型组[(15.7±1.3)%]相比,MSC移植组海马区星形胶质细胞所占面积百分比[(10.3±1.4)%]降低(P<0.05)。与模型组相比,MSC移植组自发交替率升高,认知指数升高,转棒运动时间增加(P<0.05)。与模型组(0.191±0.002)相比,MSC移植组海马区脑白质FA值(0.224±0.004)升高(P<0.05)。结论:hUC-MSC可减轻未成熟小鼠脑白质损伤程度,促进脑白质的发育,改善远期学习记忆及运动功能缺陷,其机制可能与抑制星形胶质细胞激活有关。
Aim:To investigate the effect of human umbilical cord mesenchymal stem cells(hUC-MSC)transplantation on white matter injury in immature mice.Methods:P5 C57BL/6J mice were allocated into 4 groups of 27 each.The normal control group was not treated;in the sham operation group,the common carotid artery was not transected;in the model group and MSC transplantation group,the injury model was induced by transecting the common carotid artery.The MSC transplantation group received 5×10~5 hUC-MSC injection into the lateral ventricle post-surgery.The model group received PBS instead.On day 7 post-surgery,7 mice from each group were randomly chosen and underwent MRI to assess brain injury,followed by immunohistochemical and immunofluorescence staining to analyze the expressions of microtubule-associated protein 2(MAP2)and myelin basic protein(MBP)which marking the cerebral grey matter and white matter,as well as brain tissue neurons,astrocytes,and microglia.From day 24 post-surgery,the remaining 20 mice began to undergo neurobehavioral tests,including novel object recognition,Y-maze experiment,rotarod and CatWalk gait analysis.And 7 mice were taken from each group to assess the development of white matter using DTI 120 days after surgery and fractional anisotropy(FA)was assessed.Results:In comparison with the model group,the MSC transplantation group exhibited significant reductions in cerebral infarction volume,white matter loss volume ratio,and gray matter loss volume ratio(P<0.05).The percentage of astrocytes in the hippocampus was significantly lower in the MSC transplantation group[(10.3±1.3)%]compared with the model group[(15.7±1.3)%](P<0.05).The MSC transplantation group also demonstrated significant increase in the spontaneous alternation rate,recognition index and rotarod-turning time(P<0.05).Compared with the model group(0.191±0.002),the FA of the MSC transplantation group(0.224±0.004)was elevated(P<0.05).Conclusion:hUC-MSC could alleviate the degree of white matter injury in immature mice,enhance white matter development,and improve the long-term learning memory and motor function deficits,and its neuroprotective effect may be related to inhibiting the activation of astrocytes.
作者
张含
宋娟
王军
李文冬
彭茜瑞
杨禄祥
张新玲
曹洋洋
ZHANG Han;SONG Juan;WANG Jun;LI Wendong;PENG Xirui;YANG Luxiang;ZHANG Xinling;CAO Yangyang(Department of Neonatology,the Third Affiliated Hospital,Zhengzhou University;Henan Key Laboratory for Pediatric Brain Injury,Zhengzhou 450052)
出处
《郑州大学学报(医学版)》
北大核心
2025年第2期162-166,共5页
Journal of Zhengzhou University(Medical Sciences)
基金
河南省医学科技攻关计划项目(LHGJ20210453)。
关键词
人脐带间充质干细胞
未成熟脑
脑白质损伤
缺氧缺血
行为学
小鼠
human umbilical cord mesenchymal stem cell
immature brain
white matter injury
hypoxia-ischemia
e thology
mouse
