异氟醚吸入麻醉对孕鼠子代学习记忆能力的影响
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Influence of isoflurane exposure in pregnant rats on the learning and memory of offsprings
背景与目的
每年约有2％的孕妇在全身麻醉下接受非产科手术。怀孕期间，全身麻醉可能会影响胎儿的大脑发育。本试验旨在探讨异氟醚用于孕妇对胎儿影响的安全剂量范围。
方 法
将48只SD妊娠大鼠随机分为3组，分别吸入1.3％异氟醚（Iso1组），2.0％异氟醚（Iso2组）和50％O2（对照组）3小时。他们的后代在出生后第28天和第90天接受Morris水迷宫试验，以评估学习和记忆。在其海马齿状回中检测到环磷酸腺苷反应原件结合蛋白（CREB）和磷酸化环磷酸腺苷反应原件结合蛋白（p-CREB）的表达。
结 果
与对照组相比，少数Iso2组的后代能够越过平台(P < 0.05)。因此，Iso2组后代主要在颗粒层下区表达磷酸化环磷酸腺苷反应原件结合蛋白（p-CREB），这与Iso1组和对照组后代中检测到的海马齿状回的整个颗粒细胞层都表达相反。Iso2组中磷酸化环磷酸腺苷反应原件结合蛋白（p-CREB）的表达水平也低于Iso1组和对照组(P < 0.05)。
结 论
怀孕期间吸入1.3％的异氟醚对后代的学习和记忆没有明显影响; 吸入2.0％的异氟醚将导致与海马齿状回颗粒细胞层中环磷酸腺苷反应原件结合蛋白（CREB）磷酸化抑制相关的空间记忆损伤。
原始文献摘要
Huang W, Dong Y, Zhao G, et al. Influence of isoflurane exposure in pregnant rats on the learning and memory of offsprings[J]. Bmc Anesthesiology, 2018, 18(1):5.
Background: About 2% of pregnant women receive non-obstetric surgery under general anesthesia each year. During pregnancy, general anesthetics may affect brain development of the fetus. This study aimed to investigate safe dosage range of isoflurane.
Methods: Forty-eight SpragueDawley (SD) pregnant rats were randomly divided into 3 groups and inhaled 1.3% isoflurane (the Iso1 group), 2.0% isoflurane (the Iso2 group) and 50% O 2 alone (the control group) for 3 h,respectively. Their offsprings were subjected to Morris water maze at day 28 and day 90 after birth to evaluate learning and memory. The expression of cAMP-response element binding protein (CREB) and phosphorylated cAMP-response element binding protein (p-CREB) was detected in the hippocampus dentate gyrus.
Results: Less offsprings of Iso2 group were able to cross the platform than that of the control group (P< 0.05).Accordingly, the Iso2 offsprings expressed p-CREB mainly in the subgranular zone in contrast to the whole granular cell layer of hippocampus dentate gyrus as detected in the Iso1 and control offsprings; the expression level of pCREB was also lower in the Iso2 than Iso1 or control offsprings (P< 0.05).
Conclusion: Inhalation of isoflurane at 1.3% during pregnancy has no significant influence on learning and memory of the offspring; exposure to isoflurane at 2.0% causes damage to spatial memory associated with inhibition of CREB phosphorylation in the granular cell layer of hippocampus dentate gyrus.
麻醉学文献进展分享
贵州医科大学高鸿教授课题组 编辑：王贵龙 审校：李华宇