基质细胞衍生因子-1及CXC家族趋化因子-4在人脐带间充质干细胞干预新生大鼠脑白质损伤中的作用  

Effects of stromal derived factor-1 and CXC chemokine receptor-4 in rats with white matter damage treated with human umbilical cord mesenchymal stem cells

作　　者：王诗雨[1] 朱丽华[1] 摆翔[1] 蒋犁[1] 李伟 

机构地区：[1]东南大学附属中大医院儿科,南京210009 [2]江苏省干细胞工程技术研究中心

出　　处：《中华围产医学杂志》2014年第5期329-336,共8页Chinese Journal of Perinatal Medicine

基　　金：国家自然科学基金（81370739）;江苏省科技基金（BK20131303）

摘　　要：目的 探讨基质细胞衍生因子-l（stromal derived factor-1,SDF-1）及其受体——CXC家族趋化因子-4（CXC ehemokine receptor-4,CXCR-4）在人脐带间充质干细胞（human umbilical cord mesenchymal stem cells,hUC-MSCs）定向迁移治疗早产儿脑白质损伤的可能机制. 方法 108只3日龄清洁级Sprague-Dawley大鼠随机分为实验组、对照组和假手术组.实验组和对照组大鼠结扎左侧颈总动脉并吸入氧浓度为6％的氮氧混合气体4h,假手术组仅游离左侧颈总动脉.实验组大鼠缺氧处理后24 h腹腔注射0.5 mlhUC-MSCs（1×106个/ml）.HE染色观察大鼠脑组织病理改变,分别采用免疫组织化学方法和实时荧光定量逆转录-聚合酶链反应技术检测各组大鼠5、7和14日龄时（各组各时间点6只大鼠）脑白质中SDF-1和CXCR-4蛋白及mRNA的表达情况.采用单因素方差分析及LSD检验进行统计学分析. 结果 HE染色显示,14日龄时实验组大鼠双侧脑室大小相似,未见明显细胞水肿、变性和坏死.假手术组大鼠双侧脑室形态大小均正常.对照组大鼠左侧脑室较对侧明显增大,脑室形状不规则,可见部分神经细胞变性、坏死.5、7和14日龄时,实验组大鼠脑组织SDF-1蛋白表达水平为0.15±0.06、0.24±0.01和0.12±0.01,CXCR-4蛋白表达水平为0.35±0 16、0.60±0.21和0.72±0.25;对照组大鼠脑组织SDF-1蛋白表达水平为0.13±0.01、0.16±0.01和0.08±0.01,CXCR-4蛋白表达水平为0.18±0.04、0.17±0.09和0.25±0.06;均高于假手术组（SDF-1蛋白表达水平为0.03±0.01、0.04±0.01和0.02±0.01,CXCR-4蛋白表达水平为0.04±0.02、0.05±0.03和0.05±0.03）（LSD检验,P值均＜0.05）.实验组SDF-1蛋白在7日龄时表达达高峰,14日龄时下降,在7和14日龄时均高于对照组（LSD检验,P值均＜0.05）.CXCR-4蛋白在5日龄即高于对照组,后逐渐升高,在7和14日龄表达高于5日龄,3个时间点表达水平均高于对照组（LSD检验,P值均＜0.05）.5、7和14日龄时,实�Objective To investigate the effects and the migration mechanisms of stromal derived factor-1 （SDF-1） and CXC chemokine receptor-4 （CXCR-4） in rats with white matter damage treated with human umbilical cord mesenchymal stem cells （hUC-MSCs）.Methods A total of 108 three-day old Sprague-Dawley rats were randomly divided into the experimental group,control group and sham group.The left common carotid artery was ligated and then exposed to hypoxia of 6％ O2 and 94％ N2 in rats in the experimental and control groups.Rats in sham group were neither ligation nor hypoxia.After 24 hours,rats in the experimental group were administered 0.5 ml hUC-MSCs （1 × 106/ml） intraperitoneally,and rats in control and sham groups were administered 0.5 ml saline by the same way.Immunohistochemistry and reverse transcription-polymerase chain reaction were used to determine the expression of SDF-1 and CXCR-4 protein and mRNA in 5-,7-and 14-day-old rats.Analysis of variance and the LSD test were used for statistical analysis of the data.Results HE staining showed that,in 14 day-old rats of the experimental group,bilateral cerebral ventricles were similar with no cellular edema or necrocytosis.In the sham group,bilateral cerebral ventricles were also normal.However,in the control group,ventriculomegaly,cellular degeneration and necrocytosis were observed on the left side.On the 5th,7th and 14th day,SDF-1 protein levels were 0.15±0.06,0.24±0.01 and 0.12±0.01,and CXCR-4 protein levels were 0.35±0.16,0.60±0.21 and 0.72±0.25,respectively,in the experimental group; SDF-1 protein levels were 0.13 ± 0.01,0.16± 0.01 and 0.08± 0.01,and CXCR-4 protein levels were 0.18 ± 0.04,0.17 ± 0.09 and 0.25 ± 0.06,respectively,in the control group,and all were higher than those in the sham group （SDF-1 protein levels were 0.03 ± 0.01,0.04± 0.01 and 0.02±0.01; and CXCR-4 protein levels were 0.04±0.02,0.05±0.03 and 0.05±0.03,respectively） （LSD test,all P＜0.05）.SDF-1 protein increased to a peak on the 7th day and decre

关 键 词：脑白质病 趋化因子CXCL12 受体 CXCR4 间质干细胞 脐带 动物 新生 

分 类 号：R742[医药卫生—神经病学与精神病学]