西酞普兰对睡眠障碍大鼠Nrf2/ARE/HO-1通路及学习记忆能力的影响  

Effects of citalopram on Nrf2/ARE/HO-1 pathway and learning and memory ability in rats with sleep disorder

作　　者：程闯[1] 李娟[2] 王红雷 刘国[1] CHENG Chuang;LI Juan;WANG Honglei;LIU Guo(Department of Psychiatry,Jingzhou Mental Health Center,Jingzhou 434000,China;Department of General Surgery,Jingzhou Second People's Hospital,Jingzhou 434000,China)

机构地区：[1]荆州市精神卫生中心精神科,湖北荆州434000 [2]荆州市第二人民医院普外科,湖北荆州434000

出　　处：《现代医学》2022年第11期1361-1366,共6页Modern Medical Journal

基　　金：湖北省卫生计生委指导性项目(WJ2017F106)。

摘　　要：目的:探讨西酞普兰对睡眠障碍大鼠核因子E2相关因子2(Nrf2)/抗氧化反应元件(ARE)/血红素加氧酶-1(HO-1)通路及学习记忆能力的影响。方法:将SD大鼠分为对照组(灌胃生理盐水)、模型组(建模+灌胃生理盐水)、西酞普兰低剂量组(建模+灌胃1.05 mg·kg^(-1)西酞普兰)、西酞普兰中剂量组(建模+灌胃2.1 mg·kg^(-1)西酞普兰)和西酞普兰高剂量组(建模+灌胃4.2 mg·kg^(-1)西酞普兰)。Morris水迷宫实验检测大鼠学习记忆能力,酶联免疫吸附试验测定谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)活性及丙二醛(MDA)含量,蛋白印迹法检测Nrf2、HO-1蛋白表达。结果:与对照组相比,模型组大鼠的目标象限停留时间百分比、穿越平台次数显著减少(P<0.05),逃避潜伏期显著延长(P<0.05),海马组织中GSH-Px、SOD活性及Nrf2、HO-1蛋白水平显著降低(P<0.05),MDA含量显著升高(P<0.05);随着西酞普兰的使用及剂量的升高,大鼠的逃避潜伏期缩短(P<0.05),目标象限停留时间百分比、穿越平台次数显著增多(P<0.05),海马组织中GSH-Px、SOD活性及Nrf2、HO-1蛋白水平显著升高(P<0.05),MDA含量显著降低(P<0.05)。结论:西酞普兰能提高睡眠障碍大鼠学习记忆能力,其机制可能与激活Nrf2/ARE/HO-1通路有关。Objective: To investigate the effects of citalopram on nuclear factor erythroid 2 related factor 2(Nrf2)/antioxidant response element(ARE)/heme oxygenase-1(HO-1) pathway and learning and memory ability in rats with sleep disorder. Methods: SD rats were divided into control group(intragastric administration of normal saline), model group(modeling+intragastric administration of normal saline), low-dose citalopram group(modeling+intragastric administration of 1.05 mg·kg^(-1)citalopram), medium-dose citalopram group(modeling+intragastric administration of 2.1 mg·kg^(-1)citalopram) and high-dose citalopram group(modeling+intragastric administration of 4.2 mg·kg^(-1)citalopram). The learning and memory ability of rats were detected by morris water maze test, the activity of glutathion peroxidase(GSH-Px), superoxide dismutase(SOD) and the content of malondialdehyde(MDA) in hippocampus were detected by enzyme linked immunosorbent assay, the expression of Nrf2 and HO-1 protein in hippocampus were detected by Western blot. Results: Compared with the control group, the percentage of target quadrant residence time and the frequency of crossing platform in the model group were significantly decreased(P<0.05), the escape latency time was significantly increased(P<0.05), the activities of GSH-Px and SOD, the levels of Nrf2 and HO-1 protein in hippocampus were decreased(P<0.05), the content of MDA was significantly increased(P<0.05). With the increase of citalopram dose, the escape latency time of rats was decreased(P<0.05), the percentage of target quadrant residence time and the times of crossing platform were significantly increased(P<0.05), the activities of GSH-Px and SOD, the protein levels of Nrf2 and HO-1 in hippocampus were significantly increased(P<0.05), the content of MDA was significantly decreased(P<0.05). Conclusion: Citalopram can improve the learning and memory ability of rats with sleep disorder, and its mechanism may be related to the activation of Nrf2/ARE/HO-1 pathway.

关 键 词：西酞普兰 睡眠障碍 核因子E2相关因子2/抗氧化反应元件/血红素加氧酶-1通路 学习记忆能力 

分 类 号：R364[医药卫生—病理学]