快速动眼睡眠剥夺对大鼠学习、记忆能力及海马组织自噬的影响

Effects of rapid eye movement sleep deprivation on cognitive and autophagy in rat hippocampus

目的探讨快速动眼(rapid eye movement,REM)睡眠剥夺后与大鼠认知相关的行为学变化及脑内海马组织中自噬相关蛋白的表达水平。方法健康成年雄性大鼠经过筛选后分为空白对照组(CC组)、环境对照组(TC组)、睡眠剥夺组(SD组),每组各6只;采用改良多平台睡眠剥夺法(modified multiple platform method,MMPM)建立睡眠剥夺模型,连续剥夺5 d后利用Morris水迷宫检测大鼠认知功能;用蛋白质印记法(Western Blot,WB)检测自噬相关微管蛋白(LC3)及SQSTM1/P62的表达水平变化。结果与CC组和TC组比较,SD组大鼠毛色无光泽、易激惹、体重下降(P<0.05)。SD组与其他2组比较,逃逸潜伏期延长、目标象限时间减少(P<0.05)。WB显示SD组与其他2组比较,大鼠脑内海马组织自噬相关蛋白LC3-II表达水平上升,P62水平下降(P<0.05)。CC组与TC组大鼠比较,体重、学习记忆能力、海马组织自噬蛋白表达水平均无明显差异(P>0.05)。结论睡眠剥夺后可损害大鼠学习及记忆功能,海马组织中自噬水平上调提示自噬活动可能参与睡眠剥夺介导的认知功能障碍过程。

Objective To investigate the effects of rapid eye movement（REM） sleep deprivation（SD） on the learning and memory abilities,and the changes of autophagy in the rat hippocampus.Methods Healthy adult male Sprague-Dawley（SD） rats were randomly divided into sleep deprivation（SD） group,Treatment control（TC） group and circumstance control（CC） group,and each group included 6 rats.The sleep deprivation model was established by the modified multiple platform method（MMPM）.After 5 days of measure,morris water maze was used to test the cognitive function of rats,and the hippocampal LC3-II and P62 protein levels were detected by western blot method.Results Compared with CC and TC groups,SD rats were exhausted and irritated.The weight of SD rats was considerably decreased from the third day of sleep deprivation（P〈0.05）.The escape latencies of SD group were obviously increased and rates of SD group spent significantly less time in the target quadrant than those of control group （P〈0.05）.Compared with the control group,the protein expression of LC3-II was significantly increased as P62 significantly decreased in the SD group（P〈0.05）.At the same time,there were no significant differences between the CC group and TC group.Conclusion SD could be the reason which leaded to the decrease of learning and memory abilities,increased the expression of LC3-Ⅱ and P62,elevated the formation of autophagosome,and suggested that autophagy might be involved in the cognitive impair induced by sleep deprivation.