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系统性缺氧导致新生大鼠脑损伤及远期行为异常
李 浩
(昆明医科大学基础医学院病理与病理生理学系,云南 昆明 650500)
摘要:
[摘要]目的 探讨新生0 d(P0d)SD大鼠经系统性缺氧后,远期神经行为、脑组织形态结构及脑室周围白质髓鞘碱性蛋白(MBP)表达的变化.方法 新生P0d SD大鼠40只随机分为正常对照组(NG组,n=20)和系统性缺氧组(Hy组,n=20),Hy组大鼠于出生后24 h内予以缺氧(5%O2+95%N2,28℃,3.5 h),NG组不予处理.行为学检测,观察大鼠运动反应及学习记忆能力的变化;1.5 T MRI扫描观察大鼠脑组织形态及信号改变;透射电镜观察大鼠脑室周围、胼胝体及海马CA1区超微结构改变;经SDS-PAGE电泳检测大鼠脑室周围MBP的表达变化.结果(1)Hy组大鼠拒俘实验、旷场实验、斜坡实验、悬吊实验得分降低(P<0.05),Y臂电子迷宫测试成功率下降、达标天数延长(P<0.001);(2)1.5 T MRI扫描:Hy组大鼠侧脑室扩大,胼胝体变薄,海马及脑室周围T2信号增高;(3)透射电镜:缺氧后大鼠海马神经毡水肿,神经元受损,胼胝体髓鞘层分层、溶解;(4)SDS-PAGE电泳:缺氧早期大鼠脑室周围MBP表达升高(P<0.05),3 d时下降(P<0.05).结论 经系统性缺氧诱导P0d SD大鼠缺氧缺血性脑损伤,大鼠出现脑组织形态改变、神经元受损、髓鞘化障碍及远期行为异常,与早产儿PVL相符.
关键词:  [关键词]系统性缺氧  新生大鼠  行为学  超微结构  髓鞘碱性蛋白
DOI:
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基金项目:[基金项目]国家自然科学基金资助项目(81200939,31260242);云南省科技计划项目(2011FB060);国家级大学生创新基金资助项目(201310678001)
The Changes of Long-term Behavior and Brain Morphology after Systematic Hypoxia Exposure in Neonatal Rats
LI Hao
(Dept. of Pathology and Pathophysiology,School of Basic Medical Sciences,Kunming Medical University, Kunming Yunnan 650500,China)
Abstract:
[Abstract]Objective To investigate the change of long-term behavior, brain morphology and myelin basic protein (MBP) expression after systematic hypoxia exposure in P0d neonatal rats. Methods P0d neonatal SD rats were randomly and equally divided into control group(NG group)and systematic hypoxia group(Hy group). Hy group rats were exposed to 5%O2 for 3.5h. Behavior tests were applied at P29d and P30d. 1.5T MRI scanning of brain was used to detect morphology change in P60d rats after hypoxia. The changes in ultrastructure of hippocampal CA1 and corpus callosum(CC)after hypoxia were further confirmed by transmission electron microscopy(TEM). Immunoblotting assays were performed to identify the dynamic changes of MBP. Results(1)The scores in refused captured test,open field test,slope experiments and the suspension test decreased(P < 0.05). The success rates of Y arm maze test decreased and days up to standard significantly prolonged (P < 0.001). (2)Abnormal signal in hippocampus and lateral ventricle, thinner corpus callosum were observed by 1.5T MRI scanning after hypoxia 2 months. (3)Electron microscope results revealed loosen structure and neuropil edema appeared in periventricular white matter. (4)The expression of MBP in the periventricular regions of NG group was detected by immunoblotting assay at the early development stages. Systemic hypoxia exposure to neonatal rats could decrease MBP expression after hypoxia 3 days but increase expression after hypoxia 4 hours(P < 0.05). Conclusion An obviously morphology injury which distinct located in periventricular white matter(PWM)and the abnormal of the long-term behavior can be confirmed after systematic hypoxia exposure in neonatal rats.
Key words:  [Key words]Systemic hypoxia  Neonatal rats  Behavior  Ultrastructure  Myelin basic protein