Abstract:

Objective To study the effect of hyperbaric oxygen (HBO) treatment on learning and memory ability of rats with chronic cerebral ischemia (CCI) and the mechanism. Methods 240 male SD rats were randomly divided into sham operation group, CCI group and HBO group, with 80 rats in each group. The CCI model was established by bilateral common carotid artery occlusion. Rats in HBO group were treated with HBO for 28 days (0.2 MPa, once a day, 60 minutes each time). Morris water maze test was used to evaluate the learning and memory ability of each group. The escape latency time was measured on day 7, 14, 21 and 28 after modeling (training for 3 days before each detection, 20 rats for each detection), and the crossing platform times was measured only on day 28. On day 28, HE staining, RT-PCR and Western blot were used to detect the pathological changes of neurons, the expression level of Nogo-A mRNA and Nogo-A protein in hippocampus, respectively . Results (1) Compared with the sham operation group, the escape latency time of rats in CCI group on day 7, 14, 21 and 28 were prolonged (all P <0.05), and the times of crossing platform decreased on day 28 (P <0.05). Compared with CCI group, the escape latency time of rats in HBO group were shorter on day 7, 14, 21 and 28 (all P <0.05), and the times of crossing platform increased on day 28 (P <0.05). (2) HE staining showed that neurons damage in HBO group was less than that in CCI group. (3) The expression level of Nogo-A mRNA and Nogo-A protein in the hippocampus of CCI group were higher than that in sham operation group (both P <0.05). The expression level of Nogo-A mRNA and Nogo-A protein in HBO group were lower than that in CCI group (both P <0.05). Conclusions HBO treatment could improve cognitive function in rats with chronic cerebral ischemia, and the mechanism of which may be related to the down regulation of Nogo-A expression in hippocampus of CCI rats.

Key words: Chronic cerebral ischemia; Hyperbaric oxygen; Cognitive function; Axon regeneration; Nogo-A

摘要：

目的 探讨高压氧（hyperbaric oxygen，HBO）治疗对慢性脑缺血（chronic cerebral ischemia，CCI）大鼠 学习记忆能力的影响及其作用机制。 方法 选取240只雄性SD大鼠随机分为假手术组、CCI组和HBO组，每组80只。采用双侧颈总动脉阻 断法建立CCI模型，HBO组建模12 h后开始进行HBO治疗28 d，压力0.2 MPa，每日1次，每次60 mi n。采用 Morri s水迷宫实验评估7、14、21、28 d大鼠的学习记忆能力，每个时间点20只，检测前均进行3 d训练， 记录各组大鼠的逃避潜伏时间、穿越平台次数。28 d后处死大鼠取海马组织进行HE染色评估神经元 损伤病理变化，RT-PCR法检测Nogo-A mRNA，Western blot法检测Nogo-A蛋白的表达水平。 结果 ①与假手术组比较，CCI 组7、14、21、28 d逃避潜伏时间均延长（均P＜0.05），28 d跨越平台次 数减少（P＜0.05）；与CCI 组比较，HBO组7、14、21、28 d逃避潜伏时间均缩短（均P＜0.05），28 d跨越 平台次数增加（P＜0.05）。②HE染色显示HBO组神经元损伤程度较CCI组减轻；③CCI组Nogo-A mRNA 和Nogo-A蛋白表达水平均较假手术组升高（均P＜0.05），HBO组表达水平均较CCI组下降（P＜0.05）。 结论 HBO治疗可改善慢性脑缺血大鼠认知功能，其机制可能与下调海马组织中Nogo-A的表达水平 有关。

关键词: 慢性脑缺血; 高压氧; 认知功能; 轴突再生; 轴突生长抑制因子