高压氧对缺氧缺血性脑损伤新生大鼠的远期影响

Long-term Effects of Hyperbaric Oxygen Therapy on Neonatal Rats with Hypoxic-ischemic Brain Injury

【目的】探讨早期和延迟高压氧(HBO)治疗对缺氧缺血性脑损伤(HIBD)新生大鼠的远期影响。【方法】7日龄大鼠37只随机分为对照组(n=10，假手术处理)、HIBD组(n=9)、EHBO组(n=9，HIBD模型后0.5～1h开始2个绝对大气压HBO治疗，稳压30min／次，间隔24h，连续2次)和LHBO组(n=9，HIBD模型后48～72h开始2个绝对大气压HBO治疗，稳压30min／次，间隔24h，连续5次)，以大鼠远期的学习记忆功能(Morris水迷宫实验)和海马形态组织学(海马锥体细胞层结构和CA1区存活神经元数)来判断干预效果。【结果】HIBD组大鼠的学习记忆功能严重不良伴海马结构严重受损，与对照组相比，水迷宫实验中平均逃逸潜伏期延长(56.35s与23.07s，P＜0.05)、搜索时间和搜索路程缩短(分别为29.29s与51.21s，548cm与989cm，均P＜0.05)、海马存活神经元减少(100个／mm与183个／mm，P＜0.05)；早期HBO治疗明显减轻HIBD大鼠的学习记忆功能障碍(潜伏期：39.17s与56.35s；搜索时间：36.84s与29.29s；搜索路程：686cm与548cm，P＜0.05)，并使海马存活神经元增多(131个／mm与100个／mm，P＜0.05)，延迟HBO治疗不能减轻HIBD大鼠的学习记忆功能障碍(潜伏期：56.25s与56.35s；搜索时间：30.11s与29.29s；搜索路程：572cm与548cm，P＞0.05)，海马存活神经元无增多(95个／mm与100个／mm，P＞0.05)；大鼠在水迷宫实验中的逃逸潜伏期与海马锥体细胞层存活神经元数呈直线负相关(r=-0.819，P＜0.01)。【结论】早期HBO治疗可减轻HIBD程度，并可改善HIBD所引起的远期学习记忆功能缺陷，延迟HBO治疗对HIBD无效。

[Objective] To evaluate the long-term effects of early and delayed hyperbaric oxygen （HBO） therapy on neonatal rats with hypoxic-ischemic brain injury （HIBD）. [Method] Postnatal 7 days （PD7） pups （n=37） were randomly set into 4 groups： Control （n=10, pseudo operation）, HIBD group （n=9, the left common carotid was dissected and ligated. After 1-2 h recovery, the pups were exposed to 8% oxygen-92% nitrogen gas mixture for 2 h）, EHBO group （n=9, group of early HBO therapy, pups began to HBO treatment with 2 atmosphere absolutes, 2×30 min at a 24 h intervals just 0.5-1 h after the HIBD model）, or LHBO group （n=9, group of delayed HBO therapy, pups began to HBO treatment with 2 atmosphere absolutes, 5×30 rain at a 24 h intervals just 48-72 h after the HIBD model）. For evaluating the HBO interference effect, we measured the spatial learning and memory ability in the Morris water maze, and survival neurons in CAl region of hippoearnpus. [Results] Compared with control, the rats in HIBD group displayed significant morphologically and histological deficits, as well as severe learning and memory disability. In Morris water maze, mean escape latency in HIBD group were longer （56.35 s vs.23.07s, P〈 0.05）, probe time and probe length were shorter （29.29 s vs 51.21 s and 548 cm vs 989 cm respectively, P〈 0.05）, and survival neurons in CA1 region were less （100/mm vs.183/mm, P〈 0.05）. Early HBO therapy resulted in protection against beth HIBD-induced brain tissue loss and spatial learning and memory disability （mean escape latency： 39.17 s vs 56.35 s, probe time： 36.84 s vs 29.29 s, probe length： 686 cm vs 548 cm, survival neurons： 131/mm vs 100/mm, P〈 0.05）. Delayed HBO therapy did not showed improvement of either spatial learning and memory or brain tissue loss （mean escape latency： 56.25 s vs 56.35 s, probe time： 30.11 s vs 29.29 s, probe length： 572 cm vs 548 cm, survival neurons： 95/mm vs 100/mm, P 〉0.05）. There was a close linear correlation between the CAl survival neurons and the mean escape latency for block 9 acquisition trials （r= -0.819, P〈 0.01）. [Conclusion] Early HBO therapy decreased the degree of HIBD and improved the long-term deficiency of learning and memory function induced by HIBD, but delayed HBO therapy had no effect on treating HIBD.