快速眼动睡眠剥夺引起大鼠皮质PERK活化及药物干预  

Effects of sleep deprivation on PERK activation in rat cerebral cortex and drug intervention

作　　者：郭筱华[1] 赵忠新[1] 张琳[1] 江波[1] 黄流清[1] 

机构地区：[1]第二军医大学附属长征医院神经内科,上海200003

出　　处：《中华老年心脑血管病杂志》2007年第9期630-633,共4页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：上海市科技发展基金项目(2005312)

摘　　要：目的观察不同时间快速眼动睡眠剥夺引起大鼠皮质PERK活化和磷酸化elF2α蛋白表达的变化以及依达拉奉干预的作用。方法将60只Sprague-Dawle大鼠随机分为正常对照组(5只),环境对照组(5只)和睡眠剥夺组(50只)。其中睡眠剥夺组又分为模型组,生理盐水组和依达拉奉组3个亚组。采用改良多平台睡眠剥夺法建立大鼠快速眼动睡眠剥夺模型,通过Western blot技术观察快速眼动睡眠剥夺后大鼠额叶PERK活化和磷酸化elF2α蛋白表达的变化规律,并考察依达拉奉对这些指标的影响。结果与正常对照组和环境对照组比较,不同时间快速眼动睡眠剥夺后大鼠皮质激活了磷酸化的PERK和磷酸化elF2α蛋白表达,表达水平显示了先升后降的变化规律。依达拉奉干预后两指标明显下降(P<0.01)。结论睡眠剥夺启动了内质网应激反应过程中未折叠蛋白应答通路之一,依达拉奉可能是通过减轻内质网应激而起到脑保护作用。Objective To observe the changes of PERK（double-stranded RNA-aclivated protein kinase-like endoplasmic reticulum kinase） activation and elF2α（P） （phosphorylation of the alpha subunit of eukaryotic initiation factor 2） expression in the rat cerebral cortex at different stages of rapid eye movement sleep deprivation（SD） and effects of edaravone. Methods Sixty Sprague Dawley rats were divided randomly into three groups. Of them, 5 were in normal cage control group（CC）,5 were in tank control group（ TC） and 50 were in sleep deprivation group（SD）. The SD were divided into three subgroups,including model group,saline group and edaravone group. The modified multiple platform method（MMPM） was used as the rapid eye movement（REM） sleep deprivation method. The Western blot technique was used for detecting PERK activation and elF2α（P） expression in the rats frontal cortex. Results The Western blot results showed that the expression of elF2α（P） and PERK（P） in cerebral cortex was increased after sleep deprivation. The levels of elF2α（P） and PERK（P） showed a trend from increase to decline. The administration of edaravone noticeably reduced the levels of PERK（P） and elF2α（P）,compared with the SD model group and saline treated group（ P〈0.01）. Conclusions Sleep deprivation initiated the phosphorylalion of elF2α pathway during unfolded protein response in the endoplasmic reticulum stress. Edaravone can protect against endoplasmic reticulum dysfunction in the cerebral cortex induced by REM sleep deprivation.

关 键 词：睡眠剥夺 睡眠 快速眼运动 大脑皮质 自由基清除剂 

分 类 号：R740[医药卫生—神经病学与精神病学]