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基于AMPK通路探究功能性消化不良的中医药治疗
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Abstract:
功能性消化不良(FD)是一种常见的胃肠功能性疾病，全球患病率较高，其病理机制涉及胃肠动力障碍和内脏高敏性等多重因素，临床治疗仍面临难以彻底根治的困境。近年来，腺苷酸活化蛋白激酶(AMPK)信号通路被证实可以通过影响Cajal间质细胞(ICCs)的自噬、促进ghrelin释放以及抗氧化应激等途径调节胃肠运动改善FD。本综述旨在系统性地探讨中医药通过干预AMPK信号通路来防治FD的机制，并试图揭示其在临床治疗、基础科研及新药研发领域的新视角和研究潜力。
Functional dyspepsia (FD) is a common gastrointestinal functional disorder with a high global prevalence. The pathological mechanisms involve multiple factors such as gastrointestinal dysmotility and visceral hyperalgesia, and clinical treatment still faces the dilemma of difficulty in complete cure. In recent years, the AMP-activated protein kinase (AMPK) signaling pathway has been shown to regulate gastrointestinal motility and improve FD through influencing autophagy of interstitial cells of Cajal (ICCs), promoting ghrelin release, and antioxidant stress, among other pathways. This review aims to systematically explore the mechanisms of traditional Chinese medicine in preventing and treating FD by interfering with the AMPK signaling pathway, and attempts to reveal its new perspectives and research potential in the field of clinical treatment, basic scientific research, and drug development.
| [1] | 王煜姣, 王香香, 蒋凯林, 等. 中医药治疗功能性消化不良研究进展[J]. 中国中医药信息杂志, 2023, 30(9): 187-191. |
| [2] | 孟梦, 王帅, 张声生. 《功能性消化不良中医诊疗专家共识意见(2023)》解读[J]. 中国中西医结合消化杂志, 2024, 32(7): 564-567, 574. |
| [3] | Tack, J., Schol, J., Van den Houte, K., Huang, I. and Carbone, F. (2020) Paradigm Shift: Functional Dyspepsia—A “Leaky Gut” Disorder? American Journal of Gastroenterology, 116, 274-275. https://doi.org/10.14309/ajg.0000000000001077 |
| [4] | Holczer, M., Hajdú, B., Lőrincz, T., Szarka, A., Bánhegyi, G. and Kapuy, O. (2019) A Double Negative Feedback Loop between Mtorc1 and AMPK Kinases Guarantees Precise Autophagy Induction Upon Cellular Stress. International Journal of Molecular Sciences, 20, Article 5543. https://doi.org/10.3390/ijms20225543 |
| [5] | Holczer, M., Hajdú, B., Lőrincz, T., Szarka, A., Bánhegyi, G. and Kapuy, O. (2020) Fine-Tuning of AMPK-ULK1-mTORC1 Regulatory Triangle Is Crucial for Autophagy Oscillation. Scientific Reports, 10, Article No. 17803. https://doi.org/10.1038/s41598-020-75030-8 |
| [6] | Xu, C., Song, Y., Wang, Z., Jiang, J., Piao, Y., Li, L., et al. (2021) Pterostilbene Suppresses Oxidative Stress and Allergic Airway Inflammation through AMPK/Sirt1 and Nrf2/HO-1 Pathways. Immunity, Inflammation and Disease, 9, 1406-1417. https://doi.org/10.1002/iid3.490 |
| [7] | Kaji, N., Horiguchi, K., Iino, S., Nakayama, S., Ohwada, T., Otani, Y., et al. (2016) Nitric Oxide-Induced Oxidative Stress Impairs Pacemaker Function of Murine Interstitial Cells of Cajal during Inflammation. Pharmacological Research, 111, 838-848. https://doi.org/10.1016/j.phrs.2016.07.030 |
| [8] | Mizushima, N. and Komatsu, M. (2011) Autophagy: Renovation of Cells and Tissues. Cell, 147, 728-741. https://doi.org/10.1016/j.cell.2011.10.026 |
| [9] | Bi, W.P. and Man, H.B. (2021) Baicalin Inhibits Inflammation and Apoptosis of Interstitial Cells of Cajal by Targeting the NF-κB-Mediated AMPK/ERK/Akt Pathway in an Ulcerative Colitis Rat Model. NEURO Endocrinology Letters, 42, 528-537. |
| [10] | Deng, J., Lai, M., Tan, X. and Yuan, Q. (2019) Acupuncture Protects the Interstitial Cells of Cajal by Regulating Mir-222 in a Rat Model of Post-Operative Ileus. Acupuncture in Medicine, 37, 125-132. https://doi.org/10.1177/0964528419829755 |
| [11] | Drossman, D.A. and Hasler, W.L. (2016) Rome IV—Functional GI Disorders: Disorders of Gut-Brain Interaction. Gastroenterology, 150, 1257-1261. https://doi.org/10.1053/j.gastro.2016.03.035 |
| [12] | Yagi, T., Asakawa, A., Ueda, H., Miyawaki, S. and Inui, A. (2013) The Role of Ghrelin in Patients with Functional Dyspepsia and Its Potential Clinical Relevance (Review). International Journal of Molecular Medicine, 32, 523-531. https://doi.org/10.3892/ijmm.2013.1418 |
| [13] | 唐雷, 徐派的, 张红星, 等. 电针对功能性消化不良大鼠胃窦AMPKα及mTOR的影响[J]. 中国中医急症, 2019, 28(2): 196-199. |
| [14] | Zhou, T., Yan, Y., Zhao, C., Xu, Y., Wang, Q. and Xu, N. (2019) Resveratrol Improves Osteogenic Differentiation of Senescent Bone Mesenchymal Stem Cells through Inhibiting Endogenous Reactive Oxygen Species Productionviaampk Activation. Redox Report, 24, 62-69. https://doi.org/10.1080/13510002.2019.1658376 |
| [15] | 常彦祥, 孙利平. 柴胡皂苷D对肝癌大鼠肿瘤生长和免疫功能的影响[J]. 中国临床药理学杂志, 2020, 36(14): 2059-2062. |
| [16] | 万莹, 曾毅, 吕文亮, 等. 柴胡皂苷D调控CaMKKβ/AMPK信号通路介导ICCs细胞自噬的机制[J]. 世界科学技术-中医药现代化, 2024, 26(6): 1393-1402. |
| [17] | Yu, L., Xie, X., Cao, X., Chen, J., Chen, G., Chen, Y., et al. (2021) The Anticancer Potential of Maslinic Acid and Its Derivatives: A Review. Drug Design, Development and Therapy, 15, 3863-3879. https://doi.org/10.2147/dddt.s326328 |
| [18] | Zheng, X., Zhang, S. and Chen, Q. (2025) Maslinic Acid Improves Mitochondrial Function and Inhibits Oxidative Stress and Autophagy in Human Gastric Smooth Muscle Cells. Open Life Sciences, 20, Article ID: 20221036. https://doi.org/10.1515/biol-2022-1036 |
| [19] | 李莉, 贾庆玲, 王煜姣, 等. 柴胡疏肝散对功能性消化不良大鼠胃组织线粒体功能及线粒体自噬的影响[J]. 中国实验方剂学杂志, 2021, 27(23): 26-34. |
| [20] | 白璐. 和胃理气方调节线粒体自噬治疗功能性消化不良的实验研究[D]: [博士学位论文]. 沈阳: 辽宁中医药大学, 2021. |
| [21] | 梁俊尧, 郭璇, 张德旭, 等. 舒胃汤通过AMPK/ULK1/FUNDC1信号通路调控线粒体自噬缓解功能性消化不良[J/OL]. 中药药理与临床, 1-14. https://doi.org/10.13412/j.cnki.zyyl.20250521.002, 2026-01-09. |
| [22] | 金恒, 凌家艳, 杨敏, 等. 四逆散对功能性消化不良大鼠AMPK/mTOR通路的调控作用[J]. 中国老年学杂志, 2025, 45(13): 3241-3244. |
| [23] | 李润法, 段永强, 白敏, 等. 香砂六君子汤对脾胃虚弱型功能性消化不良大鼠胃动力的作用[J]. 中成药, 2023, 45(4): 1108-1113. |
| [24] | Zeng, F., Qin, W., Ma, T., Sun, J., Tang, Y., Yuan, K., et al. (2012) Influence of Acupuncture Treatment on Cerebral Activity in Functional Dyspepsia Patients and Its Relationship with Efficacy. American Journal of Gastroenterology, 107, 1236-1247. https://doi.org/10.1038/ajg.2012.53 |
| [25] | Tang, L., Zeng, Y., Li, L., Wang, J., Peng, D., Zhang, T., et al. (2019) Electroacupuncture Upregulated Ghrelin in Rats with Functional Dyspepsia via AMPK/TSC2/Rheb-Mediated mTOR Inhibition. Digestive Diseases and Sciences, 65, 1689-1699. https://doi.org/10.1007/s10620-019-05960-5 |
| [26] | 潘小丽, 周丽, 王丹, 等. 电针“足三里”对功能性消化不良大鼠胃排空及自噬信号通路的影响[J]. 针刺研究, 2019, 44(7): 486-491. |
| [27] | 崔俊宇. 基于氧化应激研究“通经调脏”推拿法改善功能性消化不良的作用机制[D]: [博士学位论文]. 长春: 长春中医药大学, 2023. |
