昼夜节律的调节与睡眠优化：预防术后认知功能障碍的新策略
Regulation of Circadian Rhythms and Sleep Optimization: Emerging Strategies for Preventing Postoperative Cognitive Dysfunction
摘要: 术后认知功能障碍(POCD)是老年患者常见围术期并发症，昼夜节律紊乱与睡眠障碍是其关键危险因素。当前研究证实，视交叉上核功能受损、褪黑素分泌异常、外周生物钟紊乱等因素会通过加剧神经炎症、破坏血脑屏障等机制诱发POCD。临床中，光照疗法、褪黑素补充、时间限制性进食可调控昼夜节律，非苯二氮卓类药物、右美托咪定及认知行为疗法能优化睡眠，多模式干预效果更优，但存在个体化不足等问题。未来需研发个体化节律调控生物标志物、靶向生物钟基因的新型药物，并开展长期随访，以提供更精准的POCD预防策略。
Abstract: Postoperative Cognitive Dysfunction (POCD) is a common perioperative complication in elderly patients, with circadian rhythm disruption and sleep disorders as its key risk factors. Current studies confirm that factors such as suprachiasmatic nucleus (SCN) dysfunction, abnormal melatonin secretion, and peripheral circadian clock disturbance can induce POCD by mechanisms including exacerbating neuroinflammation and disrupting the blood-brain barrier. In clinical practice, light therapy, melatonin supplementation, and time-restricted feeding (TRF) can regulate circadian rhythms; non-benzodiazepine drugs, dexmedetomidine, and cognitive behavioral therapy can optimize sleep. Multi-modal interventions show better efficacy but have limitations such as insufficient individualization. In the future, it is necessary to develop biomarkers for individualized circadian regulation, new drugs targeting circadian clock genes, and conduct long-term follow-up studies to provide more precise strategies for POCD prevention.
文章引用：蒋宇辉, 王武涛, 赵玲. 昼夜节律的调节与睡眠优化：预防术后认知功能障碍的新策略[J]. 临床医学进展, 2025, 15(12): 428-439. https://doi.org/10.12677/acm.2025.15123429

参考文献

[1] Wu, W., Lin, J., Qiu, Y., Dong, W., Wan, J., Li, S., et al. (2023) The Role of Epigenetic Modification in Postoperative Cognitive Dysfunction. Ageing Research Reviews, 89, Article 101983. [Google Scholar] [CrossRef] [PubMed]
[2] Zhang, Y., Yin, Z., Zou, Z., Feng, S. and Xu, H. (2025) Nanopathways Modulating Postoperative Cognitive Dysfunction: Extracellular Vesicles. Frontiers in Cell and Developmental Biology, 13, Article ID: 1613378. [Google Scholar] [CrossRef] [PubMed]
[3] Ren, S., Yuan, F., Yuan, S., Zang, C., Zhang, Y. and Lang, B. (2022) Early Cognitive Dysfunction in Elderly Patients after Total Knee Arthroplasty: An Analysis of Risk Factors and Cognitive Functional Levels. BioMed Research International, 2022, Article ID: 5372603. [Google Scholar] [CrossRef] [PubMed]
[4] Campbell, E. and Figueiro, M.G. (2024) Postoperative Cognitive Dysfunction: Spotlight on Light, Circadian Rhythms, and Sleep. Frontiers in Neuroscience, 18, Article ID: 1390216. [Google Scholar] [CrossRef] [PubMed]
[5] Nešković, N., Budrovac, D., Kristek, G., Kovačić, B. and Škiljić, S. (2025) Postoperative Cognitive Dysfunction: Review of Pathophysiology, Diagnostics and Preventive Strategies. Journal of Perioperative Practice, 35, 47-56. [Google Scholar] [CrossRef] [PubMed]
[6] Zhao, W., Zhang, H. and Li, J. (2023) Effect of Dexmedetomidine on Postoperative Cognitive Dysfunction in Elderly Patients Undergoing Orthopaedic Surgery: Study Protocol for a Randomized Controlled Trial. Trials, 24, Article No. 62. [Google Scholar] [CrossRef] [PubMed]
[7] Li, Z., Yao, S., Cheng, M. and Chen, J. (2021) Evaluation of the Effect of Dexmedetomidine on Postoperative Cognitive Dysfunction through Aβ and Cytokines Analysis. Iranian Journal of Pharmaceutical Research, 20, 515-522.
[8] Wang, D., He, X., Li, Z., Tao, H. and Bi, C. (2024) The Role of Dexmedetomidine Administered via Intravenous Infusion as Adjunctive Therapy to Mitigate Postoperative Delirium and Postoperative Cognitive Dysfunction in Elderly Patients Undergoing Regional Anesthesia: A Meta-Analysis of Randomized Controlled Trials. BMC Anesthesiology, 24, Article No. 73. [Google Scholar] [CrossRef] [PubMed]
[9] Jiménez-Pastor, J.M., Morales-Cané, I., Rodríguez-Cortés, F.J., López-Coleto, L., Valverde-León, R., Arévalo-Buitrago, P., et al. (2025) Interaction between Clock Genes, Melatonin and Cardiovascular Outcomes from ICU Patients. Intensive Care Medicine Experimental, 13, Article No. 19. [Google Scholar] [CrossRef] [PubMed]
[10] Cui, Y., Zheng, Z., Zhou, Q., Han, X., Liu, S., Xia, T., et al. (2025) The Role of Clock Control of DRP1 Activity Involved in Postoperative Cognitive Dysfunction. Experimental Neurology, 385, Article 115140. [Google Scholar] [CrossRef] [PubMed]
[11] Wei, Y., Zhang, C., Wang, D., Wang, C., Sun, L. and Chen, P. (2022) Progress in Research on the Effect of Melatonin on Postoperative Cognitive Dysfunction in Older Patients. Frontiers in Aging Neuroscience, 14, Article ID: 782358. [Google Scholar] [CrossRef] [PubMed]
[12] Zhu, H., Zhang, L., Xiao, F., Wu, L., Guo, Y., Zhang, Z., Xiao, Y., Sun, G., Yang, Q. and Guo, H. (2023) Melatonin-Driven NLRP3 Inflammation Inhibition Via Regulation of NF-κB Nucleocytoplasmic Transport: Implications for Postoperative Cognitive Dysfunction. Inflammation, 46, 1471-1492. [Google Scholar] [CrossRef] [PubMed]
[13] Oberman, K., van Leeuwen, B.L., Nabben, M., Villafranca, J.E. and Schoemaker, R.G. (2024) J147 Affects Cognition and Anxiety after Surgery in Zucker Rats. Physiology & Behavior, 273, Article 114413. [Google Scholar] [CrossRef] [PubMed]
[14] Birnie, M.T., Claydon, M.D.B., Flynn, B.P., Yoshimura, M., Kershaw, Y.M., Demski-Allen, R.C.R., Barker, G.R.I., Warburton, E.C., Bortolotto, Z.A., Lightman, S.L. and Conway-Campbell, B.L. (2022) Circadian Regulation of Hippocampal Function Is Disrupted with Chronic Corticosteroid Treatment. bioRxiv.
[15] Sun, Z., Yang, N., Jia, X., Song, Y., Han, D., Wang, X., et al. (2022) Nobiletin Attenuates Anesthesia/Surgery-Induced Neurocognitive Decline by Preserving the Expression of Clock Genes in Mice. Frontiers in Neuroscience, 16, Article ID: 938874. [Google Scholar] [CrossRef] [PubMed]
[16] Song, C., Suo, Z., Wang, Z., Cao, J., Dong, Y. and Chen, Y. (2024) Melatonin Modulates Neuroinflammatory Response and Microglial Activation in Mice Exposed to Dim Blue Light at Night. Frontiers in Pharmacology, 15, Article ID: 1416350. [Google Scholar] [CrossRef] [PubMed]
[17] Tavares, C., Memória, C.M., da Costa, L.G.V., Quintão, V.C., Antunes, A.A., Teodoro, D., et al. (2025) Effect of Melatonin on Postoperative Cognitive Function in Elderly Patients Submitted to Transurethral Resection of the Prostate under Spinal Anesthesia. Clinics, 80, Article 100562. [Google Scholar] [CrossRef] [PubMed]
[18] Li, Y., Long, S., Yu, J., Feng, J., Meng, S., Li, Y., et al. (2025) Preoperative Sleep Deprivation Exacerbates Anesthesia/Surgery-Induced Abnormal Gabaergic Neurotransmission and Neuronal Damage in the Hippocampus in Aged Mice. Molecular Neurobiology, 62, 9385-9398. [Google Scholar] [CrossRef] [PubMed]
[19] Markovic, A., Kaess, M. and Tarokh, L. (2022) Heritability of REM Sleep Neurophysiology in Adolescence. Translational Psychiatry, 12, Article No. 399. [Google Scholar] [CrossRef] [PubMed]
[20] Mendoza-Alvarez, M., Balthasar, Y., Verbraecken, J., Claes, L., van Someren, E., van Marle, H.J.F., et al. (2025) Systematic Review: REM Sleep, Dysphoric Dreams and Nightmares as Transdiagnostic Features of Psychiatric Disorders with Emotion Dysregulation-Clinical Implications. Sleep Medicine, 127, 1-15. [Google Scholar] [CrossRef] [PubMed]
[21] Glosemeyer, R.W., Diekelmann, S., Cassel, W., Kesper, K., Koehler, U., Westermann, S., et al. (2020) Selective Suppression of Rapid Eye Movement Sleep Increases Next-Day Negative Affect and Amygdala Responses to Social Exclusion. Scientific Reports, 10, Article No. 17325. [Google Scholar] [CrossRef] [PubMed]
[22] Puech, C., Badran, M., Runion, A.R., Barrow, M.B., Cataldo, K. and Gozal, D. (2023) Cognitive Impairments, Neuroinflammation and Blood-Brain Barrier Permeability in Mice Exposed to Chronic Sleep Fragmentation during the Daylight Period. International Journal of Molecular Sciences, 24, Article 9880. [Google Scholar] [CrossRef] [PubMed]
[23] Rios, R.L., Kafashan, M., Hyche, O., Lenard, E., Lucey, B.P., Lenze, E.J., et al. (2023) Targeting Slow Wave Sleep Deficiency in Late-Life Depression: A Case Series with Propofol. The American Journal of Geriatric Psychiatry, 31, 643-652. [Google Scholar] [CrossRef] [PubMed]
[24] Keihani, A., Mayeli, A. and Ferrarelli, F. (2023) Circadian Rhythm Changes in Healthy Aging and Mild Cognitive Impairment. Advanced Biology, 7, e2200237. [Google Scholar] [CrossRef] [PubMed]
[25] Cordone, S., Scarpelli, S., Alfonsi, V., De Gennaro, L. and Gorgoni, M. (2021) Sleep-Based Interventions in Alzheimer’s Disease: Promising Approaches from Prevention to Treatment along the Disease Trajectory. Pharmaceuticals, 14, Article 383. [Google Scholar] [CrossRef] [PubMed]
[26] Hou, T., Yang, C., Lai, T., Wu, Y. and Yang, C. (2024) Light Therapy in Chronic Migraine. Current Pain and Headache Reports, 28, 621-626. [Google Scholar] [CrossRef] [PubMed]
[27] Knudsen-Clark, A.M., Mwangi, D., Cazarin, J., Morris, K., Baker, C., Hablitz, L.M., et al. (2024) Circadian Rhythms of Macrophages Are Altered by the Acidic Tumor Microenvironment. EMBO Reports, 25, 5080-5112. [Google Scholar] [CrossRef] [PubMed]
[28] Roy, J., Wong, K.Y., Aquili, L., Uddin, M.S., Heng, B.C., Tipoe, G.L., et al. (2022) Role of Melatonin in Alzheimer’s Disease: From Preclinical Studies to Novel Melatonin-Based Therapies. Frontiers in Neuroendocrinology, 65, Article 100986. [Google Scholar] [CrossRef] [PubMed]
[29] Bohlman, C., McLaren, C., Ezzati, A., Vial, P., Ibrahim, D. and Anton, S.D. (2024) The Effects of Time-Restricted Eating on Sleep in Adults: A Systematic Review of Randomized Controlled Trials. Frontiers in Nutrition, 11, Article ID: 1419811. [Google Scholar] [CrossRef] [PubMed]
[30] Ezzati, A., McLaren, C., Bohlman, C., Tamargo, J.A., Lin, Y. and Anton, S.D. (2024) Does Time‐Restricted Eating Add Benefits to Calorie Restriction? a Systematic Review. Obesity, 32, 640-654. [Google Scholar] [CrossRef] [PubMed]
[31] Kim, J.Y., Kim, W. and Lee, K. (2023) The Role of Micrornas in the Molecular Link between Circadian Rhythm and Autism Spectrum Disorder. Animal Cells and Systems, 27, 38-52. [Google Scholar] [CrossRef] [PubMed]
[32] 张野, 宋家乐, 路建. 围手术期睡眠障碍在术后认知功能障碍中作用的研究进展[J]. 中国现代医生, 2023, 61(27): 137-140.
[33] 王烨. 整形外科手术患者围术期睡眠障碍评估与术后睡眠障碍治疗[D]: [博士学位论文]. 北京: 北京协和医学院, 2022.
[34] Pettit, R.J., Gregory, B., Stahl, S., Buller, L.T. and Deans, C. (2024) Total Joint Arthroplasty and Sleep: The State of the Evidence. Arthroplasty Today, 27, Article 101383. [Google Scholar] [CrossRef] [PubMed]
[35] Ong, J.C. and Gamaldo, C. (2020) Optimizing Behavioral Sleep Strategies. Continuum, 26, 1075-1081. [Google Scholar] [CrossRef] [PubMed]
[36] Vital-Lopez, F.G., Doty, T.J. and Reifman, J. (2021) Optimal Sleep and Work Schedules to Maximize Alertness. Sleep, 44, zsab144. [Google Scholar] [CrossRef] [PubMed]
[37] Shin, M., Crouse, J.J., Byrne, E.M., Mitchell, B.L., Lind, P., Parker, R., et al. (2024) Changes in Sleep Patterns in People with a History of Depression during the COVID-19 Pandemic: A Natural Experiment. BMJ Mental Health, 27, e301067. [Google Scholar] [CrossRef] [PubMed]
[38] Li, Y., Lu, L. and Androulakis, I.P. (2024) The Physiological and Pharmacological Significance of the Circadian Timing of the HPA Axis: A Mathematical Modeling Approach. Journal of Pharmaceutical Sciences, 113, 33-46. [Google Scholar] [CrossRef] [PubMed]
[39] Park, M., Cao, Y. and Hong, C.I. (2024) Methods for Assessing Circadian Rhythms and Cell Cycle in Intestinal Enteroids. In: Solanas, G. and Welz, P.S., Eds., Methods in Molecular Biology, Springer, 105-124. [Google Scholar] [CrossRef] [PubMed]
[40] Verde, L., Galasso, M., Savastano, S., Colao, A., Barrea, L. and Muscogiuri, G. (2025) “Time” for Obesity-Related Cancers: The Role of Chrononutrition in Cancer Prevention and Treatment. Seminars in Cancer Biology, 114, 15-28. [Google Scholar] [CrossRef] [PubMed]
[41] Li, D., Zhou, T., Gao, J., Wu, G. and Yang, G. (2024) Circadian Rhythms and Breast Cancer: From Molecular Level to Therapeutic Advancements. Journal of Cancer Research and Clinical Oncology, 150, Article No. 419. [Google Scholar] [CrossRef] [PubMed]
[42] Mercadante, S. and Bellastella, A. (2024) Chrono-Endocrinology in Clinical Practice: A Journey from Pathophysiological to Therapeutic Aspects. Life, 14, Article 546. [Google Scholar] [CrossRef] [PubMed]

为你推荐