维甲酸对缺氧缺血性脑损伤新生鼠内源性神经干细胞巢蛋白表达的影响

Influence of retinoic acid on expression of nestin of endogenous neural stem cells in ischemic sides of newborn rats with hypoxic-ischemic brain injury

【目的】研究维甲酸对缺氧缺血性脑损伤(hypoxic-ischemic brain damage,HIBD)新生鼠内源性神经干细胞(NSCs)巢蛋白(Nestin)表达的影响。【方法】将56只7日龄HIBD新生SD乳鼠随机分为生理盐水组(对照组,n=28)及维甲酸治疗组(治疗组,n=28)。根据处死时相点每组分成3、7、14、21d4个小组,每小组7只。HIBD模型建立通过结扎7日龄新生SD乳鼠血管左颈总动脉后置于8%氧浓度的低氧环境中2.5h。HIBD的维甲酸治疗组在模型后开始每天腹腔注射维甲酸500μg/kg1次,对照组腹腔注射生理盐水。对各时相的神经功能缺损进行评分;采用免疫组织化学染色以及光镜技术分别对SD大鼠脑组织中的NSCs进行检测,Nestin阳性细胞标志神经干细胞,其数量增加表明神经干细胞的增殖。【结果】维甲酸治疗与对照组在各时相上的神经功能缺损评分比较差异均有显著性(P<0.01);第3、7、14d和21d在HIBD后的伤侧皮质及海马周围检出巢蛋白阳性细胞,分别在3、7d达高峰,随病程的延长而减少:维甲酸治疗组在巢蛋白阳性表达增高与对照组同时相上比较差异显著(P<0.01)。【结论】维甲酸具有促进HIBD新生鼠内源性神经干细胞巢蛋白阳性表达保持在较高水平的作用。

[Objective] To investigate influence of retinoic acid on expression of nestin of endogenous neural stem cells in ischemic sides of newborn rats with hypoxic-ischemic brain damage（HIBD）. [Methods] Totally 56 neonatal rats aged 7 d were randomly divided into two groups（hypoxic-ischemic NS control group and RA-treated group,group with 28 rats in each）. According to the time of sacrefice, 28 rats of every group were further divided randomly into four groups including third day （3 d） , the seventh day （7 d） , the fourteenth day（14 d）and the twenty-first day （21 d） , with 7 rats in each subgroup. The HIBD mode establish that left common carotid artery of the neonatal rats in hypoxic-ischemic group was ligated and subjected to inhalation of 8% oxygen for 2.5 h. intraperitoneal injection RA in treated group and NS in NS control group. NSCs from brain tissues of the rats of the two groups were determined with immunohistochemicalmethod under light microscope. Nestin cell mark NSCs. [Results] In RA-treated group, neuroiogic impairment score was significantly more than in the control groups at 3.7.14 and 21 d; there were positive nestin cells in the cortex and hippocampus at 3.7.14 d and 21 d,peaked at 3.7 d. the numbers of NSCs fall off from rats age accrete;In RAtreated group,the numbers of NSCs was significantly more than in the control groups,especiallythe was very significantly at 7.14 d and 21 d（P〈0. 01）. [Conclusion] RA can promote and keep high expression of the positive nestin of endogenous neural stem cells in ischemic sides of newborn rats with HIBD.