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-现代医学

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

单位：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

分类号：R364

出版年·卷·期（页码）：2022·41·第十一期（1361-1366）

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.

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