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【目的】探讨维甲酸对宫内缺氧幼年大鼠神经干细胞增殖及学习记忆能力的影响。【方法】孕SD大鼠制作宫内缺氧性脑损伤新生鼠模型。新生鼠随机分为对照组及维甲酸治疗组(治疗组)各10只。治疗组每只每天给予腹腔注射维甲酸500μg/kg,容积0.2 mL/次。对照组注射生理盐水0.2 mL,共10 d。30 d后进行Morris水迷宫实验,水迷宫实验结束的当天取脑组织、固定,常规石蜡切片(经海马),Nestin免疫组织化学染色神经干细胞。显微镜下观察其海马回Nestin阳性神经干细胞。【结果】治疗组大鼠海马回Nestin阳性细胞数(11.67±2.10)较对照组(4.82±0.52)明显增加(t=8.58,P<0.01);在目标象限,对照组大鼠搜索时间[(18.27±3.38)s,(10.78±2.20)s]均较治疗组[(23.12±2.16)s,(18.05±2.24)s]明显缩短(t=3.26,6.02,P均<0.01)。【结论】维甲酸可刺激宫内缺氧幼年大鼠海马神经干细胞的增殖,因此有效地改善大鼠远期的学习记忆功能。
【Objective】 To investigate the effects of retinoic acid on the proliferation and learning and memory ability of neural stem cells in young rats with hypoxia in uterus. 【Methods】 The neonatal rat model of intrauterine hypoxic brain injury was established in pregnant SD rats. Newborn rats were randomly divided into control group and retinoic acid treatment group (treatment group) of 10 each. The treatment group were given intraperitoneal injection of retinoic acid 500μg / kg, volume 0.2mL / time. The control group was injected with saline 0.2 mL for 10 days. Morris water maze test was performed 30 days later. Brain tissue was harvested on the day of water maze test, and fixed, paraffin sectioned by the hippocampus and Nestin immunohistochemical staining for neural stem cells. The hippocampus was observed under the microscope and returned to Nestin positive neural stem cells. [Results] The number of Nestin-positive cells in the hippocampus in treatment group was significantly higher than that in control group (4.82 ± 0.52, t = 8.58, P <0.01). In the target quadrant, the search time of [ 18.27 ± 3.38) s, (10.78 ± 2.20) s were significantly shorter than those in the treatment group [(23.12 ± 2.16) s, (18.05 ± 2.24) s] (t = 3.26,6.02, P <0.01). 【Conclusion】 Retinoic acid can stimulate the proliferation of hippocampus neural stem cells in neonatal rats with hypoxia, so it can effectively improve the long-term learning and memory function in rats.