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孕鼠暴露于异氟烷对后代学习和记忆的影响。

Influence of isoflurane exposure in pregnant rats on the learning and memory of offsprings.

作者信息

Huang Wei, Dong Yunxia, Zhao Guangyi, Wang Yuan, Jiang Jingjing, Zhao Ping

机构信息

Department of Anesthesiology, Shengjing Hospital of China Medical University, No. 36 SanHao Street, HePing District, ShenYang, Liaoning Province, People's Republic of China.

出版信息

BMC Anesthesiol. 2018 Jan 11;18(1):5. doi: 10.1186/s12871-018-0471-2.

Abstract

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 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.

摘要

背景

每年约2%的孕妇在全身麻醉下接受非产科手术。孕期全身麻醉药可能影响胎儿大脑发育。本研究旨在探究异氟烷的安全剂量范围。

方法

48只Sprague-Dawley(SD)孕鼠随机分为3组,分别吸入1.3%异氟烷(Iso1组)、2.0%异氟烷(Iso2组)和仅50%氧气(对照组)3小时。其后代在出生后第28天和第90天接受莫里斯水迷宫实验以评估学习和记忆能力。检测海马齿状回中cAMP反应元件结合蛋白(CREB)和磷酸化cAMP反应元件结合蛋白(p-CREB)的表达。

结果

Iso2组后代穿过平台的数量少于对照组(P<0.05)。相应地,与Iso1组和对照组后代海马齿状回颗粒细胞层整体表达p-CREB不同,Iso2组后代主要在颗粒下区表达p-CREB;Iso2组后代p-CREB的表达水平也低于Iso1组或对照组后代(P<0.05)。

结论

孕期吸入1.3%的异氟烷对后代学习和记忆无显著影响;暴露于2.0%的异氟烷会导致与海马齿状回颗粒细胞层CREB磷酸化受抑制相关的空间记忆损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6faf/5765622/4fa38d782f46/12871_2018_471_Fig1_HTML.jpg

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