中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (12): 3083-3090.doi: 10.12307/2026.708

• 组织构建临床实践 clinical practice in tissue construction • 上一篇    下一篇

静息态功能性MRI评价蓝斑-去甲肾上腺素系统介导伴有失眠抑郁症的发生机制

李仲贤1，2，3，焦梓桐1，2，3，任涵月1，2，3，张  潘1，2，3，彭  敏1，2，3，黄颖欣1，2，3，李梦瑶1，2，3，胡玥琛1，2，3，梁峻铨1，2，3，
阎路达1，2，3，符文彬3，4，周  鹏1，2，3
  

  1. 1广州中医药大学第七临床医学院，广东省深圳市  518000；2深圳市宝安区中医院，广东省深圳市  518000；3深圳市政府“医疗卫生三名工程”广东省中医院符文彬教授团队，广东省深圳市  518100；4广东省中医院，广东省广州市  510120
  • 收稿日期:2025-04-03 接受日期:2025-08-18 出版日期:2026-04-28 发布日期:2025-09-30
  • 通讯作者: 符文彬，主任医师，硕士生导师，博士生导师，深圳市政府“医疗卫生三名工程”广东省中医院符文彬教授团队，广东省深圳市 518100；广东省中医院，广东省广州市 510120 共同通讯作者：周鹏，主任医师，硕士生导师，博士生导师，广州中医药大学第七临床医学院，广东省深圳市 518000；深圳市宝安区中医院，广东省深圳市 518000；深圳市政府“医疗卫生三名工程”广东省中医院符文彬教授团队，广东省深圳市 518100
  • 作者简介:李仲贤，男，1992年生，广东省惠州市人，汉族，博士在读，主治医师，主要从事针灸治疗抑郁、失眠等心身情志疾病方面的研究。
  • 基金资助:
    国家自然科学基金项目(82305372)，项目负责人：梁峻铨；广东省重点领域研发计划项目(2020B1111100007)，项目负责人：符文彬；深圳市科技计划项目(JCYJ20230807115516032)，项目负责人：梁峻铨；深圳市宝安区中医药协会资助中医药临床研究专项项目(2023ZYYLCZX-4)，项目负责人：周鹏；深圳市宝安区中医药发展基金会项目(2022KJCX-ZJZL-1)，项目负责人：周鹏

Mechanism of depression with insomnia mediated by the locus coeruleus-norepinephrine system: an assessment based on resting-state functional magnetic resonance imaging

Li Zhongxian1, 2, 3, Jiao Zitong1, 2, 3, Ren Hanyue1, 2, 3, Zhang Pan1, 2, 3, Peng Min1, 2, 3, Huang Yingxin1, 2, 3, Li Mengyao1, 2, 3, Hu Yuechen1, 2, 3, #br# Liang Junquan1, 2, 3, Yan Luda1, 2, 3, Fu Wenbin3, 4, Zhou Peng1, 2, 3 #br#   

  1. 1The Seventh Clinical College of Guangzhou University of Chinese Medicine, Shenzhen 518000, Guangdong Province, China; 2Bao’an Traditional Chinese Medicine Hospital, Shenzhen 518000, Guangdong Province, China; 3Sanming Project of Medicine in Shenzhen, Shenzhen 518100, Guangdong Province, China; 4Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou 510120, Guangdong Province, China
  • Received:2025-04-03 Accepted:2025-08-18 Online:2026-04-28 Published:2025-09-30
  • Contact: Fu Wenbin, Chief physician, Master’s supervisor, Doctoral supervisor, Sanming Project of Medicine in Shenzhen, Shenzhen 518100, Guangdong Province, China; Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou 510120, Guangdong Province, China Co-corresponding author: Zhou Peng, Chief physician, Master’s supervisor, Doctoral supervisor, The Seventh Clinical College of Guangzhou University of Chinese Medicine, Shenzhen 518000, Guangdong Province, China; Baoan Traditional Chinese Medicine Hospital, Shenzhen 518000, Guangdong Province, China; Sanming Project of Medicine in Shenzhen, Shenzhen 518100, Guangdong Province, China
  • About author:Li Zhongxian, PhD candidate, The Seventh Clinical College of Guangzhou University of Chinese Medicine, Shenzhen 518000, Guangdong Province, China; Baoan Traditional Chinese Medicine Hospital, Shenzhen 518000, Guangdong Province, China; Sanming Project of Medicine in Shenzhen, Shenzhen 518100, Guangdong Province, China
  • Supported by:
    National Natural Science Foundation of China, No. 82305372 (to LJQ); Guangdong Provincial Key Fields Research and Development Program Project, No. 2020B1111100007 (to FWB); Shenzhen Science and Technology Program Project, No. JCYJ20230807115516032 (to LJQ); Special Project for Clinical Research of Chinese Medicine Funded by Bao'an District Traditional Chinese Medicine Association of Shenzhen City, No. 2023ZYYLCZX-4 (to ZP); Shenzhen Bao'an District Chinese Medicine Development Foundation Project, No. 2022KJCX-ZJZL-1 (to ZP)

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摘要：




文题释义：
静息态功能性MRI：在静息状态下，活跃的脑区局部血流量和含氧量增加，并可引起微弱的磁场信号变化，反映了神经元的自发活动。通过非侵入性医学影像技术捕捉，进而筛选脑不同生理、病理状态下的关键差异脑区，是研究脑功能机制的有利手段。
功能连接：在特定任务或静息状态下，大脑不同区域均存在协同性或关联性，信号活动的同步性和相关性反映了脑区之间功能层面的链接，链接强度在不同认知任务、意识状态以及疾病状态中发生变化，是研究生理、病理状态下脑网络机制的重要视角。

背景：相关研究发现，抑郁症患者外周血去甲肾上腺素水平较低，失眠患者存在去甲肾上腺素代谢紊乱现象，提示蓝斑-去甲肾上腺素系统的功能异常可能是构成抑郁失眠共病的神经生物学基础。
目的：采用静息态功能性MRI成像观察伴有失眠症状的抑郁症患者的脑干蓝斑功能连接，结合患者外周血去甲肾上腺素水平探讨伴有失眠症状抑郁症的潜在发生机制。
方法：于2023年3月至2024年9月在深圳市宝安区中医院和社会招募伴有失眠症状的抑郁症患者60例(病例组)，同期招募30例健康对照(健康对照组)，采用汉密尔顿抑郁量表17项(HAMD-17)、抑郁自评量表(SDS)、匹兹堡睡眠指数量表(PSQI)和失眠严重程度指数量表(ISI)评估所有受试者的抑郁状态和睡眠质量，静息态功能性MRI检测所有受试者蓝斑区域的功能连接，ELISA法检测外周血去甲肾上腺素水平。对上述各项指标进行组间比较，采用Pearson相关分析功能连接差异显著的脑区、外周血去甲肾上腺素水平与临床量表评分的相关性。
结果与结论：①病例组HAMD-17评分、SDS评分、PSQI评分和ISI评分均高于对照组(P < 0.05)，左侧蓝斑-左楔前叶、左侧蓝斑-左顶下小叶的功能连接值与外周血去甲肾上腺素水平低于健康受试组(P < 0.05)。Pearson相关分析显示，外周血去甲肾上腺素水平与左侧蓝斑-左楔前叶功能连接值(r=0.40，P < 0.01)、左侧蓝斑-顶下小叶功能连接值(r=0.36，P < 0.01)呈正相关，与HAMD-17评分(r=-0.42，P < 0.01)、PSQI评分(r=-0.46，P < 0.01)呈负相关；左侧蓝斑-左楔前叶功能连接值与HAMD-17评分(r=-0.41，P < 0.01)、PSQI评分(r=-0.44，P < 0.01)呈负相关，左侧蓝斑-顶下小叶功能连接值与HAMD-17评分(r=-0.29，P < 0.01)、PSQI评分(r=-0.36，P < 0.01)呈负相关。②结果表明，左侧蓝斑与左楔前叶、左顶下小叶功能连接值及外周血去甲肾上腺素水平的降低与抑郁和失眠症状的加重密切相关，提示蓝斑-去甲肾上腺素系统功能失调可能通过影响大脑默认模式网络(包括左楔前叶和左顶下小叶)的功能连接，介导伴有失眠症状的抑郁症的发生机制。

https://orcid.org/0000-0002-6403-3667(李仲贤)

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

关键词: 抑郁症, 失眠, 蓝斑, 去甲肾上腺素, 功能性MRI成像, 功能连接, 机制研究

Abstract: BACKGROUND: Studies have found that patients with depression have lower levels of norepinephrine in their peripheral blood, and patients with insomnia have norepinephrine metabolism disorders, suggesting that abnormalities in the function of the locus coeruleus-norepinephrine system may be the neurobiological basis for the comorbidity of depression and insomnia.
OBJECTIVE: Using functional magnetic resonance imaging (fMRI) to observe the functional connectivity of the brainstem locus coeruleus in patients with comorbid depression and insomnia under resting-state conditions and to investigate the potential mechanisms underlying the comorbidity by examining the relationship with peripheral norepinephrine levels. 
METHODS: From March 2023 to September 2024, 60 patients with comorbid depression and insomnia were recruited from Bao’an Traditional Chinese Medicine Hospital in Shenzhen and the general public (patient group), and 30 healthy controls were recruited during the same period (healthy control group). At baseline, the Hamilton Depression Rating Scale (HAMD-17), Self-Rating Depression Scale (SDS), Pittsburgh Sleep Quality Index (PSQI), and Insomnia Severity Index (ISI) were used to assess the participants' depression status and sleep quality. Resting-state fMRI was used to examine the functional connectivity of the brainstem locus coeruleus, and peripheral serum norepinephrine levels were measured using the enzyme-linked immunosorbent assay. Intergroup comparisons were made for all indicators, and a Pearson correlation analysis was conducted between significantly different functional connectivity regions, peripheral serum norepinephrine levels, and clinical scale scores. 
RESULTS AND CONCLUSION: (1) The HAMD-17, SDS, PSQI, and ISI scores were all higher in the patient group than in the control group (P < 0.05). The functional connectivity values between the left locus coeruleus and left precuneus, as well as between the left locus coeruleus and left inferior parietal lobule, were significantly lower in the patient group than the control group (P < 0.05). Peripheral serum norepinephrine levels were also significantly lower in the patient group than the control group (P < 0.05). Pearson correlation analysis revealed a positive correlation between peripheral serum norepinephrine levels and the functional connectivity values of the left locus coeruleus with the left precuneus and left inferior parietal lobule (r=0.40, P < 0.01; r=0.36, P < 0.01), as well as a negative correlation between peripheral serum norepinephrine levels and HAMD-17 (r=-0.42, P < 0.01) and PSQI scores (r=-0.46, P < 0.01). Moreover, the functional connectivity values of the left locus coeruleus with the left precuneus were negatively correlated with HAMD-17 (r=-0.41, P < 0.01) and PSQI scores (r=-0.44, P < 0.01), and the functional connectivity values of the left locus coeruleus with the left inferior parietal lobule were also negatively correlated with HAMD-17 (r=-0.29, P < 0.01) and PSQI scores (r=-0.36, P < 0.01). To conclude, the reduction in functional connectivity of the left locus coeruleus with the left precuneus and left inferior parietal lobule, as well as decreased peripheral serum norepinephrine levels, is closely associated with the exacerbation of depression and insomnia symptoms. This suggests that dysregulation of the locus coeruleus-norepinephrine system may mediate the mechanisms underlying comorbid depression and insomnia by affecting the functional connectivity of the brain's default mode network, including the left precuneus and left inferior parietal lobule.

Key words: depression, insomnia, locus coeruleus, norepinephrine, functional magnetic resonance imaging, functional connectivity, mechanism study

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