摘要
目的建立新生鼠缺氧缺血性脑病(HIE)动物模型,阐明HIE病程中神经干细胞(NSCs)的变化特点。方法210只7日龄新生SD乳鼠随机分为正常对照组、单纯缺氧组及缺氧缺血组,每组70只。根据处死时相点每组分成3、6h,1、3、7、14、21d等7个小组,每组10只。缺氧缺血组结扎血管后左颈总动脉后置于8%氧浓度的低氧环境中2.5h,单纯缺氧组仅缺氧2.5h。采用HE、免疫组织化学染色以及光镜技术分别对3组SD大鼠脑组织中的NSCs进行检测。结果缺氧缺血后3h出现轻度脑损伤,1d病变最严重,3、7d胶质细胞增生,14、21d出现脑萎缩。3组SD大鼠脑组织均存在NSCs,从第1天开始各组间NSCs细胞数差异有统计学意义,缺氧缺血组均低于单纯缺氧组,第3天时缺氧缺血组还低于正常对照组,第7～21天单纯缺氧组高于正常对照组。3组NSCs细胞数均有显著性动态变化,趋势也基本相似,除单纯缺氧组3d高于3h和6h外,3d内各时相点差异无统计学意义;以后随着时间延长而逐渐下降,每后一时相点低于前一时相点。结论成功建立了缺氧缺血性脑病动物模型;HIE早期NSCs增殖,随着病情的演变,NSCs开始减少,最后导致病变区的NSCs相继死亡;低氧有利于NSCs的增殖。
Objective To establish a neonatal rat model of hypoxic-ischemic encephalopathy and clarify the changing features of neural stem cells （NSCs） in episodes of hypoxic-ischemic encephalopathy（HIE） so as to provide experimental and theoretical evidences for treating HIE by applying NSCs at the appropraite time. Methods Totally 210 neonatal rats aged 7 d were divided randomly into three groups,normal control group, hypoxic group and hypoxic-ischemic group with 70 rats in each. According to the time of sacrefice, 70 rats of every group were further divided randomly into seven groups including third hour（3 h）, the sixth hour （6 h）, first day （1 d）, third day （3 d）, the seventh day （7 d）, the fourteenth day（14 d） and the twenty-first day （21 d） , with 10 rats in each subgroup. The left common carotid artery of the neonatal rats in hypoxic-ischemic group was ligated and those in the hypoxic group were subjected to inhalation of 8% oxygen for 2. 5 h. NSCs from brain tissues of the rats of the three groups were determined with HE staining and immunohistochemical method under light microscope. Results Most of neonatal rats in hypoxic-ischemic group behaved turning to the left stably 1 h after normal concentration of oxygen was given. In hypoxic-ischemic group, slight brain injury occurred at 3 h, severe brain injury appeared at 1 d,glial cells proliferated at 3 d and 7 d, brain atrophy was found at 14 d and 21 d. NSCs existed in brain tissues of rats in all the three groups. NSCs in normal control and the hypoxic group mainly distributed in hippocampus, subventricular tissues, striatum and cortex. But NSCs in hippocampus located in layers of molecule, cone cell and inner granular cell. NSCs in hypoxic-ischemic group showed obvious regional distribution, less in the regions with pathological changes. At 3 h, 6 h and 14 d, there was no difference in the number of NSCs between hypoxi and hypoxic-ischemic group. At 1 d, 3 d and 7 d, there was a highly significant difference in the number of NSCs between hypoxic and hypoxic-ischemic group. At 21 d, there was a significant difference in the number of NSCs between hypoxic and hypoxic-ischemic group, meanwhile,there was a significant difference in the number of NSCs between control and hypoxic group. At 3 d, there was a very significant difference in the number of NSCs between control and hypoxic-ischemic group. At 7 d and 21 d points ,there was a highly significant difference in the number of NSCs between control and hypoxic group. Conclusion The neonatal rat model of HIE was successfully established. NSCs increased in earlier period and decreased in later period of HIE, ultimately, NSCs located in the injured regions died one after anotner. Hypoxia induces NSCs＇ proliferation.
出处
《中华儿科杂志》
CAS
CSCD
北大核心
2005年第8期572-575,共4页
Chinese Journal of Pediatrics
