基于代谢组学探讨电针改善慢性睡眠剥夺小鼠焦虑抑郁行为的机制*

作者：段礼宁1，林叶泽2，李 敏2

单位：1.广州中医药大学第一附属医院，广东 广州 510405； 2.广州中医药大学，广东 广州 510006

引用：引用：段礼宁，林叶泽，李敏.基于代谢组学探讨电针改善慢性睡眠剥夺小鼠焦虑抑郁行为的机制[J].中医药导报,2026,32(5):7-12.

DOI：10.13862/j.cn43-1446/r.2026.05.002

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摘要：目的：基于代谢组学技术探讨电针改善慢性睡眠剥夺（CSD）小鼠焦虑抑郁样行为的作用机制。方法：将60只雄性Swiss小鼠随机分为对照组、模型组、电针组和氟西汀（FLX）组，每组15只。采用改良多平台水环境法建立CSD模型小鼠，通过悬尾实验（TST）、强迫游泳实验（FST）、旷场实验（OFT）、高架十字迷宫实验（EPM）评估电针对小鼠焦虑抑郁样行为的影响。行为学实验结束后，采集血清样本，通过酶联免疫吸附试验（ELISA）评估电针对血清促肾上腺皮质激素释放激素（CRH）、促肾上腺皮质激素（ACTH）、皮质酮（CORT）水平的影响。采集海马样本，采用非靶向代谢组学分析电针对小鼠海马内源性代谢物的影响。结果：与对照组比较，模型组小鼠TST、FST不动时间增加（P＜0.05或P＜0.01），OFT中心路程比、中心时间比、进入中心次数降低（P＜0.05或P＜0.01），EPM开放臂停留次数比、开放臂停留时间比降低（P＜0.01）。与模型组比较，电针组和FLX组小鼠TST、FST不动时间降低（P＜0.05或P＜0.01），开放臂停留次数比、开放臂停留时间比增加（P＜0.05）；电针组小鼠中心路程比、中心时间比增加（P＜0.05），进入中心次数呈增加趋势（P＞0.05）；FLX组小鼠中心路程比、进入中心次数、中心时间比降低（P＜0.05或P＜0.01）。ELISA检测结果显示，与对照组比较，模型组小鼠CRH、ACTH、CORT水平显著增加（P＜0.01）；与模型组比较，电针组和FLX组小鼠CRH、ACTH、CORT水平降低（P＜0.05或P＜0.01）。代谢组学结果显示，与对照组比较，模型组小鼠87个代谢物上调，72个代谢物含量下调；与模型组比较，电针组小鼠27个代谢物上调，23个代谢物下调。差异代谢物采用KEGG通路富集，发现电针改善焦虑抑郁样行为的作用机制可能与代谢通路、嘌呤代谢、mTOR信号通路、缬氨酸、亮氨酸和异亮氨酸生物合成、内源性大麻素通路有关。结论：电针能够改善CSD小鼠焦虑抑郁行为，其机制可能与对海马内源性代谢物的调节作用有关。

关键词：焦虑抑郁；慢性睡眠剥夺；电针；代谢组学；小鼠

Abstract：

Objective: To explore the mechanism of electroacupuncture (EA) in improving anxiety and depression like behavior in chronic sleep deprivation (CSD) mice based on metabolomics technology. Methods: Sixty Male Swiss mice were randomly divided into a control (CON) group, a model (MOD) group, an EA group and a fluoxetine (FLX) group, 15 mice in each group. A CSD mouse model was established using a improving multi platform water environment method. The effect of EA on anxiety and depression like behavior was evaluated through tail suspension experiment (TST), forced swimming experiment (FST), open field experiment (OFT) and elevated cross maze experiment (EPM). After the behavioral experiment, serum samples were collected. The effects of EA on the serum levels of corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were evaluated by enzyme linked immunosorbent assay (ELISA). Seahorse samples were collected and the effect of EA on endogenous metabolites in the hippocampus of mice was evaluated by non targeted metabolomics analysis. Results: Compared with the CON group, the MOD group showed an increase in TST and FST immobility time (P<0.05 or P<0.01), a decrease in the distance to center ratio, center time ratio, and the number of entries into center in the OFT (P<0.05 or P<0.01), and a decrease in the number of open arm entries and time spent in open arms in the EPM (P<0.01). Compared with the MOD group, the immobility time of the TST and FST in the EA group and the FLX group decreased (P<0.05 or P<0.01), while the open arm entry ratio and open arm time ratio increased (P<0.05). In the EA group, the central distance ratio and central time ratio increased (P<0.05), and the number of entries into the center showed an increasing trend (P>0.05). In the FLX group, the central distance ratio, number of entries into the center, and central time ratio decreased (P<0.05 or P<0.01). The ELISA showed that compared with the CON group, the MOD group showed increased levels of CRH, ACTH, and CORT (P<0.01). Compared with the MOD group, the levels of CRH, ACTH, and CORT decreased in the EA group and FLX group (P<0.05 or P<0.01). Metabolomics results showed that compared with the CON group, 87 metabolites were upregulated and 72 metabolites were downregulated in the MOD group. Compared with the MOD group, 27 metabolites were upregulated and 23 metabolites were downregulated in the EA group. Differential metabolites were enriched using the KEGG pathway and it was found that the protective mechanism of EA may be related to metabolic pathways, purine metabolism, mTOR signaling pathway, valine, leucine, and isoleucine biosynthesis and endogenous cannabinoid pathway. Conclusion: EA can improve anxiety and depression like behavior in CSD mice via regulating the endogenous metabolites in the hippocampus.

Key words：anxiety and depression; chronic sleep deprivation; electroacupuncture; metabolomics; mouse

发布时间：2026-05-23

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