异氟烷对孕期睡眠剥夺小鼠子代焦虑和认知功能的影响及机制  

Effects and mechanisms of isoflurane on anxiety and cognitive function in offspring of maternal sleep deprived mice

作　　者：张梦英 邱高林 夏晓琼[1] 李元海[1,2] ZHANG Mengying;QIU Gaolin;XIA Xiaoqiong;LI Yuanhai(Department of Anesthesiology,The Affiliated Chaohu Hospital of Anhui Medical University,Hefei,Anhui 238000,China)

机构地区：[1]安徽医科大学附属巢湖医院麻醉科,安徽合肥238000 [2]安徽医科大学第一附属医院麻醉科,安徽合肥230022

出　　处：《淮海医药》2024年第6期551-556,共6页Journal of Huaihai Medicine

基　　金：国家自然科学基金青年科学基金项目(82101349);安徽医科大学研究生科研与实践创新项目(YJS20230202)。

摘　　要：目的:探究幼年期异氟烷暴露对孕期睡眠剥夺小鼠子代成年期焦虑和认知功能的影响及机制。方法:选取孕15 d健康c57BL/6J小鼠32只,采用随机数字表法分为4组(n=8):对照组(Con组)、孕期睡眠剥夺组(MSD组)、子鼠幼年期异氟烷暴露组(Con-ISO组)、孕期睡眠剥夺+子鼠幼年期异氟烷暴露组(MSD-ISO组)。MSD、MSD-ISO组母鼠在孕15~21 d进行连续7 d的睡眠剥夺(12:00~18:00),Con、Con-ISO组母鼠不进行睡眠剥夺;Con-ISO、MSD-ISO组子鼠在出生后7 d吸入1.5%异氟烷6 h, Con、MSD组子鼠置于100%的氧气环境中6 h。子鼠出生后90 d,采用旷场实验、高架十字迷宫实验评价子鼠焦虑情绪,采用Morris水迷宫实验评价子鼠学习记忆能力。采用ELISA法检测子鼠海马炎症因子[白细胞介素-6(IL-6)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)]含量。结果:与Con组子鼠相比,Con-ISO、MSD、MSD-ISO组子鼠进入中心区域运动时间及次数、进入开臂时间及次数、靶象限游泳路程及时间百分比、穿越平台次数、海马炎症因子(IL-1β、IL-6、TNF-α)水平均下降,游泳路程增加,差异均有统计学意义(P<0.05);与Con-ISO、MSD组子鼠比较,MSD-ISO组子鼠进入中心区域运动时间及次数、进入开臂时间及次数、靶象限游泳路程及时间百分比、穿越平台次数、海马炎症因子(IL-1β、IL-6、TNF-α)水平进一步下降,游泳路程进一步增加,差异均有统计学意义(P<0.05);子鼠海马炎症因子(IL-1β、IL-6、TNF-α)水平与Con-ISO、MSD、MSD-ISO组子鼠的进入中心区滞留时间及次数、开臂滞留时间及次数、空间探索期的游泳路程及时间百分比、穿越平台次数呈负相关,而与Con-ISO、MSD、MSD-ISO组子鼠定位航行期的游泳路程呈正相关(P<0.05)。结论:幼年期异氟烷暴露加剧孕期睡眠剥夺小鼠的子代成年期的焦虑和认知功能障碍,其机制可能与海马炎症因子增加有关。Objective:To investigate the effects of isoflurane exposure in infancy on anxiety and cognitive functions in adult offspring mice of maternal sleep deprivation(MSD),and the mechanisms in it.Methods:32 healthy c57BL/6J pregnant mice were divided into 4 groups(n=8)using the random number table method:a control group(Con group),a maternal sleep deprivation group(MSD group),an isoflurane exposure of neonatal offspring mice group(Con-ISO group),and a maternal sleep deprivation+isoflurane exposure of neonatal offspring mice group(MSD-ISO group).Pregnant mice in the MSD group and the MSD-ISO group were subjected to sleep deprivation(12:00~18:00)for 7 consecutive days from day 15 to day 21 of gestation,while pregnant mice in the Con group and the Con-ISO group were not subjected to sleep deprivation.The neonatal offspring mice in the Con-ISO group and the MSD-ISO group were exposed to 1.5%isoflurane for 6h,and neonatal offspring mice in the Con group and the MSD group were exposed to 100%oxygen for 6 hours.On postnatal 90 day,the offspring mice were evaluated for anxiety using the open field test and elevated plus maze test,and the offspring mice were analyzed for learning and memory ability using the Morris water maze test.The levels of interleukin(IL)-6,IL-1βand tumor necrosis factor(TNF)-αin hippocampal tissues of offspring mice were measured by enzyme linked immunosorbent assay.Results:Compared with the Con group,the time spent in and the number of entries into the central area,the time spent in and the number of entries into the open arms,the percentage of target quadrant swimming distance and the time of swimming in the target quadrant,the number of crossing the platform,and the levels of hippocampal inflammatory factors IL-1β,IL-6 and TNF-αwere decreased,while the swimming distance covered was increased in the CON-ISO group,the MSD group and the MSD-ISO group(P<0.05).Compared with the Con-ISO group and the MSD group,the time spent in and the number of entries into the central area,the time spent in and the num

关 键 词：孕期睡眠剥夺 异氟烷 焦虑 认知功能 神经炎症 

分 类 号：R395.2[哲学宗教—心理学] R971.2[医药卫生—医学心理学]