Orexin A及其受体在睡眠剥夺影响大鼠学习记忆能力中的作用

The role of Orexin A and its receptor in sleepdeprivation affecting learning and memory of rats

目的探讨Orexin A及其受体在睡眠剥夺影响大鼠学习记忆中的作用。方法首先采用间歇性跑步机对大鼠进行72h全睡眠剥夺后下观察丘脑Orexin A的表达,然后用慢病毒载体介导siRNA沉默双侧海马Orexin A受体OX1R/OX2R基因,将健康成年雄性Wistar大鼠随机分为空白对照(CC)、环境对照(TC)、睡眠剥夺(SD)、空病毒(LV)和慢病毒基因沉默组(OXR)。Morris水迷宫试验检测各组大鼠的空间学习记忆能力。结果与TC组相比,SD组大鼠下丘脑Orexin A的表达增加,水迷宫试验逃避潜伏期明显延长,穿越平台象限的次数减少(P<0.05);与LV组相比,OXR组大鼠逃避潜伏期缩短,穿越平台象限的次数增加(P<0.05),LV组与SD组相比,差异无统计学意义(P>0.05)。结论睡眠剥夺诱导大鼠下丘脑Orexin A表达增加,空间学习记忆功能下降,慢病毒载体介导siRNA沉默海马OX1R/OX2R基因能部分逆转。

Objective To investigate the role of Orexin A and its receptor in the effect of sleep deprivation on learning and memory.Methods The expression of Orexin A in hypothalamus was observed after 72h total sleep deprivation and then the gene of Orexin A receptor in bilateral hippocampus was silenced by lentivirus vector mediated siRNA.Healthy adult male Wistar rats were randomly divided into cage control(CC),treadmill control(TC),sleep deprivation(SD),SD treated with LV-control-siRNA(Control siRNA),and SD treatedwith LV-OXR-siRNA(OXR-siRNA).Morris water maze test was used to detect the spatial learning and memoryof rats in each group.Results Compared with the TC group,the expression of Orexin A in hypothalamus of SD group was increased,the escape latency of water maze test was significantly prolonged,and the times of crossing platform quadrant were decreased(P<0.05);compared with the TC group,the escape latency of lentivirus gene silencing group was shorter,and the times of crossing platform quadrant was increased(P<0.05).There was no significant difference between SD and Control siRNA group(P>0.05).Conclusion SD can increase the expression of Orexin A in hypothalamus and decrease the spatial learning and memory of rats.Lentiviral vector mediated siRNA silencing of Orexin A receptor in hippocampus can partially reverse this phenomenon.