Orexin受体功能在睡眠剥夺大鼠空间学习记忆和海马齿状回细胞增殖中的作用  

Effects of orexin receptors on the spatial learning and memory and proliferation of dentate gyrus cells in rats with sleep deprivation

作　　者：苗素云 倪丽艳[1,3] 王利 宋立敏 唐吉友[1] MIAO Suyun;NI Liyan;WANG Li;SONG Limin;TANG Jiyou(Department of Neurology,Qianfoshan Hospital Affiliated to Shandong University,Jinan 250014,Shandong,China;Department of Neurology,Central Hospital of Taian,Taian 271000,Shandong,China;People's Hospital of Juye County,Juye 274900,Shandong,China;Department of Traditional Chinese Medicine and Western Medicine,Yuhuangding Hospital of Yantai,Yantai 264000,Shandong,China)

机构地区：[1]山东大学附属千佛山医院神经内科,山东济南250014 [2]泰安市中心医院神经内科,山东泰安271000 [3]巨野县人民医院神经内科,山东巨野274900 [4]烟台毓璜顶医院中医中西医结合科,山东烟台264000

出　　处：《山东大学学报（医学版）》2019年第1期41-47,54,共8页Journal of Shandong University:Health Sciences

基　　金：国家自然科学基金(81471345)

摘　　要：目的探讨慢病毒载体介导siRNA沉默海马orexin-1受体(OX1R)和orexin-2受体(OX2R)基因对睡眠剥夺大鼠空间学习记忆及海马齿状回细胞增殖的影响。方法经过筛选后的40只健康成年雄性Wistar大鼠随机分为空白对照组、环境对照组、睡眠剥夺组、空病毒组和慢病毒介导组,每组8只。采用间歇性跑步机对睡眠剥夺组、空病毒组和慢病毒介导组进行72 h全睡眠剥夺。通过Morris水迷宫实验检测各组大鼠的空间学习记忆能力,并采用共聚焦技术观察海马齿状回区BrdU^+、BrdU^+/NeuN^+细胞表达。结果与环境对照组相比,睡眠剥夺组逃避潜伏期明显延长,穿越平台象限的次数减少(P<0.05),海马齿状回区BrdU^+、BrdU^+/NeuN^+细胞表达减少(P<0.05);与空病毒组相比,慢病毒介导组逃避潜伏期缩短,穿越平台象限的次数增加(P <0. 05),海马齿状回区BrdU^+、BrdU^+/NeuN^+细胞表达增多(P<0.05),但空病毒组与睡眠剥夺组相比,差异无统计学意义(P>0.05)。结论睡眠剥夺能引起大鼠空间学习记忆功能受损,慢病毒载体介导siRNA沉默海马OX1R/OX2R基因能改善睡眠剥夺大鼠的空间学习记忆能力,可能与促进海马齿状回区神经细胞的增殖和分化有关。Objective To investigate the effects of lentivirus mediated siRNA silencing hippocampal orexin-1 receptor( OX1R) and orexin-2 receptor( OX2R) genes on the spatial learning and memory and the proliferation of dentate gyrus cells in sleep-deprived rats. Methods A total of 40 healthy adult male Wistar rats were screened and randomly divided into cage control group,treadmill control group,sleep deprivation group,lentivirus group and lentivirus mediated group,with 8 rats in each group. Rats in the sleep deprivation,lentivirus and lentivirus-mediated groups ran intermittently on treadmills for 72 hours for sleep deprivation. The spatial learning and memory ability of all rats was investigated with Morris water maze. The numbers of bromodeoxyuridine-labelled( BrdU^+) cells,and BrdU^+/NeuN^+cells were quantified with a confocal laser-scanning microscope. Results Compared with the treadmill control group,the sleep deprivation group showed significantly prolonged escape latency,decreased times across platform,and reduced numbers of BrdU^+and BrdU^+/NeuN^+cells( P<0.05). Compared with the lentivirus group,the lentivirus-mediated group showed shortened escape latency,increased times across platform( P<0.05),and increased numbers of BrdU^+and BrdU^+/NeuN^+cells( P<0.05). No significant differences were observed between the lentivirus group and sleep deprivation group( P > 0.05).Conclusion Sleep deprivation can impair the spatial learning and memory,and inhibit the proliferation of cells in dentate gyrus. Lentiviral mediated siRNA silencing of OX1R/OX2 R genes can improve the spatial learning and memory ability of sleep-deprived rats,which may be related to the proliferation and maturation of neural cells in dentate gyrus.

关 键 词：睡眠剥夺 orexin受体 海马 学习记忆 神经细胞再生 

分 类 号：R741[医药卫生—神经病学与精神病学]