α-硫辛酸对睡眠剥夺所致的大鼠脑中IRE1表达的影响
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全军医学科学技术研究“十一五”计划保健专项课题(07BJZ06);上海市科技发展基金(08411950700);第二军医大学长征医院 “三重三优”学科人才建设基金(2005312).


Effects of α-lipoic acid on cerebral IRE1 expression induced by sleep deprivation in rats
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Supported by grants from the Health Care Special Project of “11 Five-Year Plan” for Chinese Military Medical Science and Technology Research (07BJZ06),the Shanghai Science and Technology Development Foundation (08411950700) and the Key Superior Program of Changzheng Hospital(2005312).

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    摘要:

    目的:观察睡眠剥夺及抗氧化药物干预对大鼠皮质、海马中抑制阻抗性酯酶1(IRE1)表达的影响。方法:将SD大鼠随机分为对照组和睡眠剥夺组。对照组分为空白对照组(CC,n=10)和实验环境对照组(TC,n=10)。睡眠剥夺组制作不同时间睡眠剥夺大鼠模型(SD,n=120),分为用药组(25 mg·kg-1·d-1α-硫辛酸)和非用药组,每组按不同睡眠剥夺(SD)及恢复时间(RS)随机分为6小组:SD 1 d、SD 3 d、SD 5 d、SD 7 d、SD 7 d/RS 6 h、SD 7 d/RS 12 h(n=10)。应用RT-PCR和免疫组织化学方法检测IRE1转录及蛋白表达变化。结果:RT-PCR结果发现大鼠海马、皮质中IRE1 mRNA表达量在CC组和TC组间无统计学差异,SD组明显升高(P<0.05),用药后随之减少。将用药组分别与非用药组相应时间点作一一比较,在睡眠剥夺5、7 d及恢复睡眠后6、12 h各时间点有统计学意义(P<0.05),其余无统计学意义。经免疫组织化学染色后,有棕黄色阳性细胞表达,各组间的表达水平与RT-PCR结果一致。结论:α-硫辛酸能够降低睡眠剥夺大鼠脑内IRE1的表达,为睡眠剥夺的抗氧化治疗研究提供了依据。

    Abstract:

    Objective:To observe the influences of sleep deprivation and antioxidant agent α-lipoic acid on the expression of IRE1 in the cortex and hippocampus in rats.Methods: Rats were randomly divided into control groups and sleep deprivation group.The control groups included blank control group (n=10) and environmental control group (n=10).Sleep deprivation group included 120 rats,and rats were further divided into α-lipoic acid group (25 mg·kg-1·d-1) and sleep deprivation model group.The two were further divided into 6 groups according to the periods of sleep deprivation and sleep restoration (SD 1 d,SD 3 d,SD 5 d,SD 7 d,SD 7 d/RS 6 h,SD 7 d/RS 12 h\[n=10\]).The expression of IRE1 mRNA and protein was examined by RT-PCR and immunohistochemistry,respectively.Results: RT-PCR results showed that the expression of IRE1 mRNA in the cortex and hippocampus were significantly higher in sleep deprivation group than in the blank and environmental control groups (P<0.05); there was no significant difference between the latter 2 groups.α-lipoic acid decreased the expression of IRE1.Expression of IRE1 between α-lipoic acid groups and sleep deprivation model groups was significantly different on SD 5 d,SD 7 d,SD 7 d/RS 6 h and SD 7 d/RS 12 h(P<0.05).The immunohistochemistry results of IRE1 expression were consistant with RT-PCR results.Conclusion: α-lipoic acid can reduce the cerebral IRE1 expression in sleep deprivation rats,which provides a basis for antioxidant treatment of sleep deprivation.

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  • 收稿日期:2008-07-22
  • 最后修改日期:2008-10-26
  • 录用日期:2009-04-01
  • 在线发布日期: 2009-05-22
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