睡眠剥夺诱发氧化应激反应研究进展
第二军医大学学报A cad J S ec M il
M ed Uni v
!2007
Feb ;28(2>
-201!-
?综!述?
睡眠剥夺诱发氧化应激反应研究进展
江!波!赵忠新"(第二军医大学长征医院神经内科 上海200003>
!摘要"!睡眠剥夺作为一种应激源!类似于饥饿"缺氧等!可造成机体正常生理功能紊乱!引起免疫功能下降"学习记忆能力下降及情绪障碍等#氧化应激普遍存在于细胞内!与衰老"阿尔茨海默病"帕金森病等多种神经系统变性疾病相关#目前有研究表明睡眠剥夺可通过多种途径诱发机体的氧化应激!具体包括睡眠剥夺后导致能量消耗代谢及自由基的增多"机体抗氧化能力降低以及通过内质网应激间接引起氧化应激三条途径!本文就此作一综述#!关键词"!睡眠剥夺$
氧化应激!中图分类号"!R 395.2!!!!文献标识码"!A !!!!文章编号"!0258-879X (2007>02-0201-03
O xi dative stress i nduced b y s lee p de p rivati on :an u p date
JI ANG Bo Z ~AO Zhon g -xi n "(D e p art m ent of Neur ol o gy Chan g zhen g ~os p ital S econd M ilitar y M edical Uni versit y Shan g hai 200003 Chi na >
[ABS TRACT ]!S l ee p de p ri vati on as a stress ust li ke star vati on and anoxi a can i nduce t he p h y si ol o g ical f uncti on chan g es such as e moti on disor ders co g niti on disor ders and i mmune disor ders .Oxi dati ve stress is co mmon i n cells and is cl osel y rel ated t o a g i n g A lzhei m er disease Paki nson diseases e t c .Previ ous st udi es sho Wed t hat sl ee p de p ri vati on coul d i nduce oxi dati ve stress U i a diff erent p at h Wa y s na m el y t he i ncrease of t he m etabolic rate and f ree radicals t he de p ress of anti oxi dant abilit y and t he i ndirect eff ects of endo p l as m ic reticul u m stress .In t his revi e W We su mm arize t he recent p r o g ress on t he above fi el ds .[KEY WORDS ]!slee p de p ri vati on ;oxi dati ve stress
[A cad J S ec M il M ed Uni v 2007 28(2>:201-203]
!基金项目"!上海市科技发展基金(024119029>;第二军医大学长征医院 十一五 三重三优 学科人才建设计划基金.Su pp ort ed b y t he Shan g hai
S ci ence
T echnol o gy
D evel o p m ent
Foundati on
(024119029>and t he Ke y Su p eri or Pr o g ra m of Chan g z hen g ~os p it al .
!作者简介"!江!波 硕士 主治医师.E -m ail : i an g bo304!126.co m
"
Corres p ondi n g aut hor .E -m ail :z haozx !m ed m ail .co https://www.wendangku.net/doc/a92222885.html,
!!现代社会中人们睡眠时间呈逐渐减少趋势 许多情况如工作~疾病等因素常导致睡眠剥夺(sl ee p de p ri vati on SD > 睡眠剥夺已成为睡眠障碍的一种表现形式0睡眠剥夺对机体可造成危害 临床及动物试验均表明睡眠剥夺可引起一系列综合征:进食增多及体重下降 能量消耗增多 血清儿茶酚氨类激素增多 免疫功能下降及条件性致病菌感染机会增加等
[1-3]
晚期可出现致命性败血症
[4]
0氧化应激普遍存在于
细胞内 与多种神经系统变性疾病相关 近年来有不少有关睡眠剥夺与氧化应激关系的研究 本文综述如下0l !细胞的氧化及抗氧化系统
!!细胞主要的氧化物包括活性氧簇(reacti ve ox yg en s p e-ci es ROS >及活性氮簇(reacti ve nitr o g en s p eci es RNS > ROS 主要是线粒体电子链传递中的副产品 同时也与烟酰胺腺嘌呤二核苷酸磷酸(nicoti na m i de adeni ne di nucl eoti de p hos-p hate NADP ~>氧化酶~黄嘌呤氧化酶等有关 RNS 主要与一氧化氮合酶有关[5-6]0机体的抗氧化防御系统主要包括抗氧化酶和抗氧化复合物 抗氧化酶包括超氧化物歧化酶(su-p er oxi de dis mutase SOD >~谷胱甘肽过氧化物酶(g l utat hi one p er oxi dases GS~-PX >~过氧化氢酶及谷胱甘肽还原酶(g l u-tat hi one reductase GS~-R >等 其中SOD 又包括含铜~锌超氧化物歧化酶(Cu /Zn-SOD >及含锰超氧化物歧化酶(M n-SOD >0抗氧化复合物主要包括还原型谷胱甘肽~维生素C ~维生素E 及食物中的黄酮类等[7]0另外机体内的一部分游
离氨基酸~多肽及蛋白质在维持较高浓度时可发挥低水平的抗氧化活性[5]0正常情况下机体内的氧化物与抗氧化系统保持着动态的平衡0当各种因素导致ROS 等自由基生成过多或抗氧化防御系统功能降低 ROS 等可对细胞脂质~蛋白质~DNA 等造成氧化破坏 引起氧化应激[8]02!睡眠剥夺与氧化应激产物的关系
!!目前有证据表明睡眠剥夺可诱发机体的氧化应激0S
il-va 等[9]
利用多平台技术对大鼠进行72h 睡眠剥夺后发现睡
眠剥夺组海马脂质过氧化物丙二醛(m aleic di al deh y de MDA 被认为是一种氧化应激的敏感标记物>水平较对照明显增多 而褪黑素或维生素E 等抗氧化剂可降低睡眠剥夺组海马MDA 水平[10]0国内唐庆娟等[11]利用转盘法给以大鼠连续72h 完全睡眠剥夺后发现血浆MDA 增多 提示机体受到氧化损害 D e oli veri a 等[12]对W istar 大鼠进行96h 选择性快速眼动睡眠剥夺(RE M -SD >后发现既往已经建立的氧化应激的重要指标-
--血浆硫代巴比妥酸反应物质(t hi o-
-202!-第二军医大学学报!2007年2月,第28卷
bar bit uric aci d reacti ve substances,TBARS>/谷胱甘肽[13],睡眠剥夺组明显高于对照组
3!睡眠剥夺诱发氧化应激的机制
!!关于睡眠剥夺诱发氧化应激的机制主要有以下几种
<1>睡眠剥夺后能量代谢增加导致ROS等自由基产生过多
<2>机体抗氧化防御系统能力降低<3>睡眠剥夺后内质网应激间接激活氧化应激等本文就上述几个方面分别加以叙述
3.1!能量代谢及自由基产量的增加!许多研究表明睡眠剥夺后机体处于高代谢状态,能量消耗增加,临床表现为进食增多及体质量下降等[1,14-16],同时也有报道认为睡眠剥夺可引起糖原的减少及自由基产量的增加[17]Everson等[18]发现大鼠RE M-SD10d时进食量较剥夺前增加了77%,剥夺10d恢复睡眠2d后体质量仍较剥夺前减少了16%Koban 等[19]发现大鼠RE M-SD20d时平均食物摄入较剥夺前增加了120%,平均丧失了其剥夺前体质量的11%,同时与代谢有关的指标氧消耗较基线增加了66%,由此证明RE M-SD 大鼠代谢率明显增高同时血浆中的一种降低食欲的激素瘦素
3.2!机体抗氧化防御系统能力降低!睡眠剥夺后可引起抗氧化防御系统能力降低D A l m ei da等[25]使用改良多平台技术在对大鼠睡眠剥夺96h后发现睡眠剥夺组鼠下丘脑谷胱甘肽水平与环境对照及空白对照组相比分别下降了18%及31%,丘脑谷胱甘肽水平与空白对照组相比也有明显下降Ra m anat han等[26]对大鼠进行了5"11d不等的RE M-SD,发现海马及脑干的Cu/Zn-SOD酶活性较对照组明显下降,而在氧化应激条件下过量的ROS具有抑制SOD活性的能力[27],考虑Cu/Zn-SOD酶活性下降可能与睡眠剥夺后过量产生的ROS有关,由此可能形成正反馈循环加速ROS的聚集对蛋白等造成氧化损伤S il va等[9]利用多平台技术对大鼠进行72h睡眠剥夺后发现睡眠剥夺组与对照组相比海马谷胱甘肽总量减少的同时氧化型谷胱甘肽
3.3!内质网应激交叉激活氧化应激!既往研究表明睡眠剥夺可引起内质网应激
!!综上所述,睡眠剥夺后可通过自由基产生过多.细胞抗氧化能力降低途径及内质网应激途径引起氧化应激目前有部分学者对睡眠剥夺后引起氧化应激持否定态度,主要考虑目前的实验条件无法完全排除其他实验因素对结果的干扰,如水平台睡眠剥夺模型中的水刺激.固定化刺激及寒冷刺激等因素也可作为应激因素对实验结果产生影响,同时睡眠剥夺选择性引起不同脑区抗氧化能力下降的具体机制等问题仍不明了,上述问题需要在以后的研究中加以明确
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!收稿日期"!2006-09-04!!!修回日期"!2007-01-15 !本文编辑"!曹!静
睡眠剥夺诱发氧化应激反应研究进展
作者：江波， 赵忠新， JIANG Bo， ZHAO Zhong-xin
作者单位：第二军医大学长征医院神经内科,上海,200003
刊名：
第二军医大学学报
英文刊名：ACADEMIC JOURNAL OF SECOND MILITARY MEDICAL UNIVERSITY
年，卷(期)：2007,28(2)
被引用次数：11次
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10.杨红梅.王黎.陈洁.李宜培.裴瑞灵芝多糖肽对Alzheimer样大鼠海马超微结构和抗氧化能力的影响[期刊论文]-中国老年学杂志 2009(18)
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12.王朔.李晓莉.唐泽瀛.宋蕾.龙梅军事应激实验动物模型研究进展[期刊论文]-武警医学院学报 2010(10)
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