α-硫辛酸对睡眠剥夺所致的大鼠脑中IRE1表达的影响

Effects of α-lipoic acid on cerebral IRE1 expression induced by sleep deprivation in rats

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(25mg.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:SD1d、SD3d、SD5d、SD7d、SD7d/RS6h、SD7d/RS12h(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IRE1mRNA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、7d及恢复睡眠后6、12h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。

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 RTPCR and immunohistochemistry, respectively. Results.. RT-PCR results showed that the expression of IRE1 mRNA in the cortex and hippoeampus 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.