高压氧对HIBD新生大鼠学习记忆功能及海马CA1区神经元的远期影响

Hyperbaric Oxygen Improves Long-term Learning-memory Deficits and Brain Injury in Neonatal Rat with Hypoxia-ischemia Brain Damage

目的探讨高压氧(hyperbaric oxygen,HBO)对缺氧缺血性脑损伤(hypox ia-ischem ia bra in dam age,H IBD)新生大鼠远期的学习记忆功能和海马CA 1区神经元的保护作用。方法18只7日龄SD大鼠随机分为3组(n=6),分别是:假手术组、H IBD组、HBO干预组(HBO+H IBD)。基于R ice法制作H IBD模型,H IBD+HBO组大鼠在H IBD后1 h应用2.5 ATA(1 ATA=100 kPa)的高压氧进行一次性治疗,治疗时间为1.5 h。在大鼠6周龄时,应用抑制性回避实验评价其短时程记忆功能,用M orris水迷宫实验评价大鼠8周龄时的空间学习和记忆功能。9周龄时灌注取脑,观察大鼠海马CA 1区的神经元死亡和丢失情况。结果在抑制性回避实验中,各组大鼠在学习期跳台潜伏期差异没有统计学意义,在测试期,H IBD+HBO组大鼠的跳台潜伏期长于H IBD组(P<0.05);在M orris水迷宫实验中,H IBD+HBO组大鼠无论在定位航行实验中还是在空间探索实验中均比H IBD组表现良好,在定位航行实验中,各组大鼠的寻台潜伏期随着实验次数的增多而逐渐缩短,而H IBD+HBO组的平均寻台潜伏期比H IBD组短(P<0.05);在空间探索实验中,无论是站台区探索时间还是穿越站台区的次数,H IBD+HBO组均优于H IBD组(P<0.05)。H IBD+HBO组大鼠的脑组织病理变化比H IBD组轻,且损伤侧的海马CA 1区的神经元没有明显的死亡和丢失。结论新生大鼠H IBD后1 h给予单次高压氧(2.5 ATA,1.5 h)治疗,可以有效地改善大鼠远期的学习记忆功能,同时也可以减轻大鼠海马CA 1区的神经元的坏死与丢失。

Objective To investigate the effect of hyperbaric oxygen （HBO） on long-term learning-memory disabilities and brain injury induced by hypoxia-ischemia in neonatal rat. Methods In the study, eighteen rats aged seven days were divid into three groups： ① sham-operated group （SHAM）, ② hypoxia-ischemia group （HIBD）, ③HBO-treated hypoxia-ischemia group （HIBD＋ HBO）. In hypoxia-ischemia groups, left common carotid artery was ligated permanently on the seventh postnatal day, two hours after the procedure; hypoxia （92% nitrogen and 8% oxygen） was induced for 2 h. In HBO-treated hypoxia-ischemia group, single HBO （2.5 ATA, 1.5 h） was administered at one hour after the hypoxia period. At the six weeks old, step-down inhibitory avoidance test was used to evaluate the short-term memory of rats. Learning and long-term spatial memory deficits were tested using Morris water maze at eight weeks old of rats. Rats were then perfused and brains removed for macroscopic and microscopic evaluation. The cell density of hippocampus were used to evaluate the degree of brain injure. Results In HIBD＋HBO group, the latency to step down the platform was significantly longer than that of HIBD group （P〈0. 05）; in HIBD＋HBO group, the mean latencies to reach the platform was significantly shorter than that of HIBD group （P〈0. 05）; in HIBD＋ HBO group, the time spent in the target quadrant was significantly lower than that in HIBD group （P〈0. 05）. Histopathological evaluation demonstrated that HBO also significantly diminished brain injury and decreased the cell loss of hippocampal CA1 region. Conclusion Single HBO （2.5 ATA, 1.5 h） can significantly improve long-term learning-memory deficits and attenuate brain injury in rats with hypoxia-ischemia brain damage.