新生大鼠长时间暴露于七氟烷对注意缺陷多动障碍的影响

陈明凯; 欧梦婵; 郝学超; 黄瀚; 张东航; 陈媛媛; 梁鹏; 周诚; 李羽

doi:10.12182/20210360601

新生大鼠长时间暴露于七氟烷对注意缺陷多动障碍的影响

Effect of Long-time Postnatal Exposure to Sevoflurane on Causing Attention-deficit/Hyperactivity Disorder in Rats

摘要

摘要:
目的探讨新生大鼠长时间吸入七氟烷是否导致注意缺陷多动障碍（attention-deficit/hyperactivity disorder，ADHD）相关的反常活动和记忆损害。
方法将出生后5 d（postnatal day 5，P5）的SD大鼠随机分为七氟烷组和对照组，分别采用吸入3%的七氟烷和吸入相同流量纯氧2 h、4 h建立七氟烷吸入麻醉模型及处理对照组。采用旷场实验（open field test，OFT）、5项选择连续反应时间任务实验（5-choice serial reaction time task，5-CSRTT）、场景恐惧（fear-conditioning，FC）实验、水迷宫（morris water maze，MWM）实验评估青少年期大鼠（～P25）和成年大鼠（～P65）的认知、记忆、焦虑及ADHD相关行为等变化。
结果在OFT中，七氟烷2 h、4 h组大鼠P21、P61活动水平和探索行为指标与对照组的差异均无统计学意义；5-CSRTT实验结果显示，七氟烷组在P25和P65时ADHD相关行为（不成熟反应次数、正确率、遗漏率）与对照组比较，差异也无统计学意义；在FC实验中，与对照组相比，七氟烷4 h暴露组大鼠僵直时间缩短，僵直潜伏期时间延长（P=0.029）；MWM实验结果显示，与对照组相比，七氟烷4 h组大鼠训练过程中逃逸潜伏期在第二天和第三天延长（P<0.05），七氟烷组平均游泳速度在P69和P76时差异无统计学意义，七氟烷4 h组的目标象限停留时间缩短（P=0.039），目标象限移动距离百分比降低（P=0.048）。
结论新生大鼠七氟烷吸入麻醉4 h后，可致记忆损害但并未增加发生ADHD相关反常活动的风险。

Abstract:
Objective To investigate whether long-term exposure to inhaled sevoflurane, a volatile anesthetic, causes abnormal activities and memory impairment related to attention-deficit/hyperactivity disorder (ADHD) in neonatal rats.
Methods On postnatal day 5 (P5), Sprague-Dawley rats were randomly assigned to two sevoflurane subgroups and two control subgroups and underwent experimental intervention. The two sevoflurane (SEVO) subgroups were exposed to 3% sevoflurane for 2 h and 4 h respectively, while the two control subgroups were given pure oxygen for the same amount and duration. Behavioral tests, including open-field test (OFT), five-choice serial reaction time task (5-CSRTT), fear-conditioning (FC) and Morris water maze (MWM), were applied to evaluate changes in cognition, memory, anxiety and ADHD-related behavioral changes in the rats in adolescence (-P25) and in adulthood (-P65).
Results In OFT, the SEVO 2 h and SEVO 4 h subgroups displayed activity level and exploratory behaviors similar to those of the control subgroups on P21 and P61, with no statistically significant difference identified in the data. 5-CSRTT results on P25 and P65 indicated no statistically significant difference between the SEVO subgroups and the control subgroups in regard to ADHD-related abnormal behaviors, including number of immature reaction, rate of correct response and omission rate. In the FC experiment, SEVO 4 h group had a shorter freezing period and longer period of freezing latency (P=0.029) in comparison to the control groups. The results of the MWM test showed that the escape latency period of rats in the SEVO 4 h group was significantly prolonged on the second day and the third day, compared to the control groups (P<0.05). The average swimming speed of SEVO groups did no exhibit any statistically significant difference on P69 or P76. The time the SEVO 4 h group spent in the target quadrant was significantly shorter than that of the control group (P=0.039) and percentage of distance traveled in the target quadrant was significantly reduced compared to that the control group (P=0.048).
Conclusion The findings suggest that four hours of inhaled sevoflurane exposure in neonate rats may cause memory impairment, but does no increase risks for ADHD-related abnormal activities.

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