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[产后长期暴露于七氟醚对大鼠患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].

作者信息

Chen Ming-Kai, Ou Meng-Chan, Hao Xue-Chao, Huang Han, Zhang Dong-Hang, Chen Yuan-Yuan, Liang Peng, Zhou Cheng, Li Yu

机构信息

Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041, China.

Department of Anesthesiology, West China Second University Hospital, Sichuan University, Chengdu 610041, China.

出版信息

Sichuan Da Xue Xue Bao Yi Xue Ban. 2021 Mar;52(2):207-215. doi: 10.12182/20210360601.

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 ( =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 ( <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 ( =0.039) and percentage of distance traveled in the target quadrant was significantly reduced compared to that the control group ( =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.

摘要

目的

研究新生大鼠长期吸入挥发性麻醉剂七氟醚是否会导致与注意力缺陷多动障碍(ADHD)相关的异常活动和记忆障碍。

方法

在出生后第5天(P5),将Sprague-Dawley大鼠随机分为两个七氟醚亚组和两个对照组,并进行实验干预。两个七氟醚(SEVO)亚组分别暴露于3%七氟醚2小时和4小时,而两个对照组给予相同量和持续时间的纯氧。应用行为测试,包括旷场试验(OFT)、五选择连续反应时任务(5-CSRTT)、恐惧条件反射(FC)和莫里斯水迷宫(MWM),以评估青春期(-P25)和成年期(-P65)大鼠的认知、记忆、焦虑和ADHD相关行为变化。

结果

在旷场试验中,SEVO 2小时和SEVO 4小时亚组在P21和P61时的活动水平和探索行为与对照组相似,数据中未发现统计学显著差异。P25和P65时的5-CSRTT结果表明,SEVO亚组和对照组在与ADHD相关的异常行为方面,包括未成熟反应次数、正确反应率和遗漏率,没有统计学显著差异。在恐惧条件反射实验中,与对照组相比,SEVO 4小时组的冻结期较短,冻结潜伏期较长(P = 0.029)。莫里斯水迷宫测试结果表明,与对照组相比,SEVO 4小时组大鼠在第二天和第三天的逃避潜伏期显著延长(P < 0.05)。SEVO组在P69或P76时的平均游泳速度没有显示出任何统计学显著差异。SEVO 4小时组在目标象限花费的时间显著短于对照组(P = 0.039),并且在目标象限行进的距离百分比与对照组相比显著降低(P = 0.048)。

结论

研究结果表明,新生大鼠吸入七氟醚4小时可能会导致记忆障碍,但不会增加与ADHD相关异常活动的风险。

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