孕晚期睡眠剥夺对孕鼠胎盘炎症、犬尿氨酸途径及幼鼠认知功能的影响  

Influence of sleep deprivation in late pregnancy on placental inflammation and the kynurenine pathway in pregnant rats and the cognitive function of young rats

作　　者：陈光雪 陈武娟 王璐 郑秀丽 Chen Guangxue;Chen Wujuan;Wang Lu;Zheng Xiuli(Beijing Jishuitan Hospital,Capital Medical University;Department of Obstetrics and Gynecology,The Fifth Affiliated Hospital of Sun Yat-sen University)

机构地区：[1]首都医科大学附属北京积水潭医院,北京102208 [2]中山大学附属第五医院妇产科,珠海519000

出　　处：《重庆医科大学学报》2024年第10期1095-1101,共7页Journal of Chongqing Medical University

摘　　要：目的:探究孕晚期睡眠剥夺对孕鼠胎盘炎症、犬尿氨酸途径及幼鼠认知功能的影响。方法:24只孕18 d大鼠随机分为对照组和模型组,每组12只。水平台睡眠剥夺法建立睡眠剥夺模型,模型组接受为期72 h的睡眠剥夺,对照组不进行睡眠剥夺,正常饲养。建模完成后,对照组与模型组随机取6只孕鼠乙醚麻醉,腹主动脉采血,完整取出脑组织,剥离胎鼠、胎盘,其余6只自然分娩,正常饲养。于幼鼠出生后34 d、64 d进行行为学检测,苏木精-伊红(hematoxylin eosin,HE)染色观察胎盘组织形态,免疫荧光染色观察胎鼠海马小胶质细胞形态和神经元增殖情况。高效液相色谱法检测色氨酸、犬尿氨酸、犬尿喹啉酸(kynurenic acid,KYNA)水平。测定母鼠血浆皮质酮与胎盘组织细胞因子水平。结果:与对照组相比,模型组幼鼠64 d旷场实验活动总距离、34 d中央区域停留时间、64 d中央区域活动距离存在差异(P<0.05),34 d高架十字迷宫实验幼鼠进入开放臂的时间增多(P<0.05),进入闭合臂的时间减少(P<0.05),64 d强迫游泳实验幼鼠不动时间增加(P<0.05)。对照组胎盘结构清晰,细胞形态正常,模型组胎盘部分滋养细胞皱缩,呈空网状,血窦减少。与对照组相比,模型组胎鼠海马神经元增殖、突起数量减少(P<0.05),小胶质细胞数量增多(P<0.05),细胞表面积增大(P<0.05),胎盘色氨酸、犬尿氨酸、KYNA、白细胞介素-1β(inter⁃leukin-1β,IL-1β)、白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、胎鼠脑组织KYNA、母鼠血浆皮质酮水平升高(P<0.05)。结论:孕晚期睡眠剥夺可能通过犬尿氨酸途径引发孕鼠胎盘炎症反应,影响幼鼠认知功能。Objective:To investigate the influence of sleep deprivation in late pregnancy on placental inflammation and the kynurenine pathway in pregnant rats and the cognitive function of young rats.Methods:A total of 24 rats pregnant for 18 days were randomly divided into control group and model group,with 12 rats in each group.The method of water platform sleep deprivation was used to establish a model of sleep deprivation;the rats in the model group received sleep deprivation for 72 hours,while those in the control group was fed normally without sleep deprivation.After modeling,6 pregnant rats were randomly selected from each group for ether anesthesia,and blood samples were collected from the abdominal aorta;brain tissue was completely removed,and stripping of fetal rats and placenta were performed.The remaining 6 rats in each group were subject to natural labor and normal feeding.Behavioral tests of the young rats were performed on days 34 and 64 days after birth;HE staining was used to observe the histomorphology of placenta,and immunofluorescent staining was used to observe the morphology of microglial cells and the proliferation of neurons in the hippocampus of fetal rats;high-performance liquid chromatography was used to measure the levels of tryptophan,kynurenine,and kynurenic acid(KYNA);the levels of plasma corticosterone and cytokines in pla⁃cental tissue were measured for maternal rats.Results:There were significant differences between the control group and the model group in total activity distance of the open field test on day 64,the time spent in the central area on day 34,and activity distance in the central area on day 64(P<0.05),and compared with the control group,the model group had a significant increase in the time of enter⁃ing the open arm(P<0.05)and a significant reduction in the time of entering the closed arm(P<0.05)in the elevated plus maze test on day 34,as well as a significant increase in immobility time in the forced swimming test on day 64(P<0.05).The control group had a clear structure

关 键 词：孕晚期 睡眠剥夺 炎症 犬尿氨酸途径 认知功能 

分 类 号：R715.3[医药卫生—妇产科学] R748[医药卫生—临床医学]