妊娠中期接触七氟醚对幼鼠学习和记忆的影响：母体锻炼的有益作用
祝贺贵州医科大学麻醉学院15级科学学位研究生赊玉琦顺利毕业
研究方向：麻醉与器官保护 指导老师：高鸿教授
研究生期间共发表文章3篇，其中北图核心2篇
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Effects of Sevoflurane Exposure During Mid-Pregnancy on Learning and Memory in Offspring Rats: Beneficial Effects of Maternal Exercise.
背景与目的
胎儿接触全身麻醉药物可能会有严重的神经认知风险，但是减轻这些有害影响的方法仍不清楚。因此，我们开始评估在大鼠怀孕期间单次或重复接触七氟醚是否会引发大鼠后代的长期认知障碍。由于怀孕期间的母体锻炼已经证明可以改善后代的认知能力，我们假设怀孕期间的母体通过跑步机锻炼可以预防由七氟醚-诱发的神经毒性。
方 法
在第一个实验中，怀孕大鼠在妊娠期（G）第14天的时候吸入3%的七氟醚2h，或者连续在G13、G14和G15天时吸入七氟醚2 h。在第二个实验中，整个怀孕期间，运动组的妊娠大鼠每天强制在跑步机上跑60分钟。使用TrkB的拮抗剂ANA-12来研究脑源性神经营养因子（BDNF）/TrkB/akt信号通路是否与母体运动所提供的神经保护有关。
结 果
我们的数据表明重复吸入七氟醚，会导致胎儿大脑组织和出生后幼鼠的海马体中的组蛋白乙酰化和BDNF表达减少。还会导致树突棘数量减少，空间依赖性学习和记忆功能障碍。这些影响通过母体的运动得到了缓解，但TrkB的拮抗剂ANA-12消除了母体运动的有益影响。
结 论
在妊娠中期的大鼠重复吸入七氟醚会导致后代长期的学习和记忆功能障碍。母鼠运动后通过加强组蛋白乙酰化和激活BDNF/TrkB/Akt下游信号，减轻幼鼠神经认知障碍。
原始文献摘要
Abstract:Fetal exposure to general anesthetics may pose significant neurocognitive risks but methods to mitigate against these detrimental effects are still to be determined. We set out, therefore, to assess whether single or repeated in utero exposure to sevoflurane triggers long-term cognitive impairments in rat offspring. Since maternal exercise during pregnancy has been shown to improve cognition in offspring, we hypothesized that maternal treadmill exercise during pregnancy would protect against sevoflurane
induced neurotoxicity. In the first experiment, pregnant rats were exposed to 3% sevoflurane for 2 h on gestational (G) day 14, or to sequential exposure for 2 h on G13, G14 and G15. In the second experiment, pregnant rats in the exercise group were forced to run on a treadmill for 60 min/day during the whole pregnancy. The TrkB antagonist ANA-12 was used to investigate whether the brain-derived neurotrophic factor (BDNF)/TrkB/Akt signaling pathway is involved in the neuroprotection afforded by maternal exercise. Our data suggest that repeated, but not single, exposure to sevoflurane caused a reduction in both histone acetylation and BDNF expression in fetal brain tissues and postnatal hippocampus. This was accompanied by decreased numbers of dendritic spines, impaired spatial-dependent learning and memory dysfunction. These effects were mitigated by maternal exercise but the TrkB antagonist ANA-12 abolished the beneficial effects of maternal exercise. Our findings suggest that repeated, but not single, exposure to sevoflurane in pregnant rats during the second trimester caused long-lasting learning and memory dysfunction in the offspring. Maternal exercise ameliorated the postnatal neurocognitive impairment by enhancing histone acetylation and activating downstream BDNF/TrkB/Akt signaling.
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