基础医学与临床 ›› 2026, Vol. 46 ›› Issue (7): 975-981.doi: 10.16352/j.issn.1001-6325.2026.07.0975

• 研究论文 • 上一篇    下一篇

舒眠胶囊缓解模型大鼠慢性睡眠剥夺所致学习记忆障碍

韩松晏, 李文华, 赵海晴, 严妍, 刘雁勇, 杨楠*   

  1. 中国医学科学院北京协和医学院 基础医学研究所 药理学系, 北京 100005
  • 收稿日期:2026-03-30 修回日期:2026-04-27 发布日期:2026-06-23
  • 通讯作者: *yangnan@ibms.pumc.edu.cn
  • 基金资助:
    中国医学科学院医学与健康科技创新工程(2021-I2M-1-020)

Shumian capsule alleviates learning and memory impairment caused by chronic sleep deprivation in mouse models

HAN Songyan, LI Wenhua, ZHAO Haiqing, YAN Yan, LIU Yanyong, YANG Nan*   

  1. Department of Pharmacology, Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100005, China
  • Received:2026-03-30 Revised:2026-04-27 Published:2026-06-23
  • Contact: *yangnan@ibms.pumc.edu.cn

摘要: 目的 探讨舒眠胶囊(SMC)对慢性睡眠剥夺致学习记忆障碍的作用及机制。方法 以雄性C57BL/6J小鼠为研究对象,采用改良多平台睡眠剥夺方法(MMPM)建立慢性睡眠剥夺(CSD)模型。采用戊巴比妥钠睡眠实验、Barnes迷宫实验、旷场实验(OFT)和强迫游泳实验(FST)分析评估小鼠睡眠、学习记忆以及精神行为等变化;采用Western blot检测 alpha2A-肾上腺素受体(α2A-AR)、TWIK相关钾离子通道2(TREK2) 和 蛋白激酶A(PKA) 催化亚基等蛋白的表达水平。结果 与模型组相比,高剂量SMC能够显著降低入睡潜伏期(P<0.05);低、中、高剂量SMC作用后均能够显著延长睡眠时间(L-SMC组、M-SMC组、H-SMC组P<0.001)。Barnes迷宫实验中,CSD小鼠在连续训练3 d后寻洞潜伏期显著增加(P<0.001),中、高剂量 SMC作用后寻洞潜伏期均显著降低,其中高剂量SMC作用最为显著(P<0.001)。在OFT中,CSD小鼠中心场停留时间显著增加(P<0.001),给药组小鼠中心场停留时间均显著减少(L-SMC组P<0.05,M-SMC组P<0.01,H-SMC组P<0.001)。在用于评估抑郁状态的FST实验中,高剂量SMC组不动时间相比模型组显著减少(P<0.001)。CSD小鼠前额叶皮层中,α2A-AR和TREK2蛋白水平显著升高(P<0.05),SMC作用逆转了这一升高趋势。这一结果提示SMC可能通过抑制α2A-AR/TREK2通道介导的皮层神经元的超极化从而改善学习记忆损伤。结论 SMC能够改善睡眠障碍以及学习记忆障碍。其中,高剂量SMC改善学习记忆障碍的作用最为显著。SMC可能通过抑制α2A-AR/TREK2通路调节神经元兴奋性,进而改善学习和记忆障碍。

关键词: 舒眠胶囊(SMC), 慢性睡眠剥夺, 学习和记忆障碍, α2A-肾上腺素受体

Abstract: Objective To investigate the effect of Shumian capsule (SMC) on learning and memory impairment induced by chronic sleep deprivation and to explore its underlying mechanism. Methods A chronic sleep deprivation (CSD) model was established with a modified multiple platform method (MMPM). The pentobarbital sodium sleep test, Barnes maze test, open field test (OFT), and forced swimming test (FST) were conducted for behavioral analysis. Western blot was used to detect the expression level of alpha2A-adrenergic receptor (α2A-AR), TWIK- related potassium channel 2(TREK2),and protein kinase A (PKA) catalytic subunit. Results Compared with the model group, high-dose SMC significantly reduced sleep onset latency (P<0.05); low-, medium-, and high-dose SMC all significantly prolonged sleep time (L-SMC, M-SMC, and H-SMC groups, P<0.001). In the Barnes maze test, after three consecutive days of training, CSD mice showed a significantly increased latency to find the target hole (P<0.001). Treatment with medium- and high-dose SMC significantly reduced the latency, with the most pronounced effect observed in the high-dose SMC group (P<0.001). In the open field test (OFT), the time spent in the center zone was significantly increased in CSD mice (P<0.001), while all SMC-treated groups showed significantly reduced center zone time (L-SMC group, P<0.05; M-SMC group, P<0.01; H-SMC group, P<0.001). In forced swimming test (FST), used to assess depressive-like behavior, the immobility time was significantly reduced in the high-dose SMC group compared with the model group (P<0.001). In the prefrontal cortex of CSD mice, the protein levels of α2A-AR and TREK2 were significantly increased (P<0.05)and SMC treatment reversed this increase. Conclusions SMC might improve learning and memory impairment by inhibiting α2A-AR/TREK2 channel-mediated hyper polarization of cortical neurons. SMC alleviates sleep disturbances and learning and memory impairments. High-dose SMC exhibits the most significant effect in improving learning and memory impairment. SMC may enhance learning and memory by modulating neuronal excitability via the inhibition of the α2A-AR/TREK2 pathway.

Key words: Shumian capsule (SMC), chronic sleep deprivation, learning and memory impairment, alpha2A-adrenergic receptor

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