缺血启动未成熟大鼠脑白质内源性修复功能的研究  

Endogenous self-repair in immature white matter induced by ischemia in neonatal rats

作　　者：李文娟[1] 陈惠金[1] 钱龙华[1] 毛凤霞[1] 

机构地区：[1]上海交通大学医学院附属新华医院/上海市儿科医学研究所,上海200092

出　　处：《中国当代儿科杂志》2012年第7期548-553,共6页Chinese Journal of Contemporary Pediatrics

基　　金：国家自然科学基金(No.81070989)

摘　　要：目的探讨缺血启动未成熟脑白质的内源性修复机制。方法 5日龄Sprague-Dawley新生大鼠随机分为假手术(Sham)组和PVL组。分别于建模后7 d及21 d光镜、电镜下评估脑白质病变及髓鞘形成情况,免疫组化检测脑白质O4+少突胶质细胞(OL)前体,观察SVZ区祖细胞的激活、增殖、迁移和分化情况。结果与Sham组比较,PVL组在建模后7 d和21 d光镜下脑白质病理均呈轻或重度病变;病理评分均明显增高;髓鞘形成数量明显减少,厚度变薄;免疫组化显示O4+OL前体明显减少。建模48 h后,PVL组SVZ区BrdU、NG2共阳性祖细胞明显增殖并向脑室周围迁移,至7 d达到高峰;从72 h开始,脑室周围出现呈BrdU、O4共阳性OL前体,至21 d,新生OL前体明显多于同时段Sham组。结论缺血可启动新生大鼠脑白质的内源性修复机制,诱导SVZ区胶质源性神经祖细胞激活、增殖、迁移至脑室周围和分化为OL前体。Objective To study in vivo the endogenous self-repair mechanism in immature white matter induced by ischemia in neonatal rats with periventricular leukomalacia （PVL）. Methods Five-day-old neonatal Spragne-Dawley （SD） rats were randomly divided into sham and PVL groups. Rat model of PVL was prepared by ligation of the right common carotid artery following 2 hours of exposure to 8% oxygen. Pathological changes and myelination in the white matter were assessed under light and electron microscopy at 7 and 21 days after PVL. O4-positive OL precursor cells in the white matter were determined with immunofluorescence staining. Activation, proliferation, migration and differentiation of glial progenitor cells in SVZ were observed using immunofluorescent double labeling of either NG2 （marker of progenitor cells） and 5-bromodeoxyuridine （ BrdU）, or 04 （ marker of OL precursor cells） and BrdU. Results All rats in the PVL group manifested either mild or severe white matter injury under light microscopy, and had higher pathological scores of white matter compared with the sham group at 7 and 21 days after PVL （P 〈 0.05 ）. Electron microscopy showed that the number and thickness of myelin sheath in the PVL group were significantly reduced compared with the sham group （P 〈0.01 ）. O4-positive OL precursor ceils in the white matter observed under fluorescence microscopy were significantly reduced in the PVL group compared with the sham group （ P 〈 0.05 ）. BrdU/NG2-positive cells in the SVZ increased significantly in the PVL group 48 hours after PVL and migrated into the periventricular area, reaching a peak on day 7 after PVL. BrdU/O4-positive newborn ceils began to appear in the periventricular area 72 hours after PVL, and the number of BrdU/O4-positive cells in the PVL group was statistically more than in the sham group on day 21 after PVL （P 〈 0.05 ）. Conclusions Ischemia may induce brain self-repair in neonatal rats, resulting in activation and proliferation of NG2 glial progenitor c

关 键 词：脑室周围白质软化 NG2神经祖细胞 新生大鼠 

分 类 号：R722.6[医药卫生—儿科]