神经调控在肝脏疾病的研究进展
Research Progress on Neuromodulation in Liver Diseases
DOI: 10.12677/acm.2024.1441230, PDF,   
作者: 任天星*, 陈 标, 黄昆鹏, 梅博升, 张博文, 张进祥#:华中科技大学同济医学院附属协和医院,湖北 武汉
关键词: 神经调控肝脏疾病神经递质Neuromodulation Liver Disease Neurotransmitters
摘要: 肝脏神经系统通过释放各种神经递质直接参与肝脏正常生理功能的调节,对维持机体稳态至关重要,同时也参与了肝脏疾病的发生与发展过程,本文主要综述神经调控在肝脏疾病发生发展中的作用,旨在深化对于神经调控在肝脏生理功能中的作用的理解,探讨在肝脏疾病中的作用机制,为肝脏疾病的预防和治疗提供理论支持和新思路。
Abstract: The hepatic nervous system is directly involved in the regulation of normal liver physiological functions through the release of various neurotransmitters, which is crucial to the maintenance of body homeostasis, and is also involved in the process of the occurrence and development of liver diseases. This paper focuses on the review of the role of neuromodulation in the occurrence and development of liver diseases, with the aim of deepening the understanding of the role of neuromodulation in the physiological function of the liver, exploring the mechanism of the role of neuromodulation in liver diseases, and providing theoretical support and new ideas for the prevention and treatment of liver diseases.
文章引用:任天星, 陈标, 黄昆鹏, 梅博升, 张博文, 张进祥. 神经调控在肝脏疾病的研究进展[J]. 临床医学进展, 2024, 14(4): 1819-1827. https://doi.org/10.12677/acm.2024.1441230

参考文献

[1] Devarbhavi, H., Asrani, S.K., Arab, J.P., et al. (2023) Global Burden of Liver Disease: 2023 Update. Journal of Hepatology, 79, 516-537. [Google Scholar] [CrossRef] [PubMed]
[2] Xiao, J., Wang, F., Wong, N.K., et al. (2019) Global Liver Disease Burdens and Research Trends: Analysis from a Chinese Perspective. Journal of Hepatology, 71, 212-221. [Google Scholar] [CrossRef] [PubMed]
[3] Mizuno, K. and Ueno, Y. (2017) Autonomic Nervous System and the Liver. Hepatology Research, 47, 160-165. [Google Scholar] [CrossRef] [PubMed]
[4] Yi, C.X., La Fleur, S.E., Fliers, E., et al. (2010) The Role of the Autonomic Nervous Liver Innervation in the Control of Energy Metabolism. Biochimica et Biophysica Acta, 1802, 416-431. [Google Scholar] [CrossRef] [PubMed]
[5] Koike, N., Tadokoro, T., Ueno, Y., et al. (2022) Development of the Nervous System in Mouse Liver. World Journal of Hepatology, 14, 386-399. [Google Scholar] [CrossRef] [PubMed]
[6] Jensen, K.J., Alpini, G. and Glaser, S. (2013) Hepatic Nervous System and Neurobiology of the Liver. Comprehensive Physiology, 3, 655-665. [Google Scholar] [CrossRef] [PubMed]
[7] Zhang, B., Vogelzang, A. and Fagarasan, S. (2022) Secreted Immune Metabolites That Mediate Immune Cell Communication and Function. Trends in Immunology, 43, 990-1005. [Google Scholar] [CrossRef] [PubMed]
[8] Akiyoshi, H., Gonda, T., Terada, T. (1998) A Comparative Histochemical and Immunohistochemical Study of Aminergic, Cholinergic and Peptidergic Innervation in Rat, Hamster, Guinea Pig, Dog and Human Livers. Liver, 18, 352-359. [Google Scholar] [CrossRef] [PubMed]
[9] Lelou, E., Corlu, A., Nesseler, N., et al. (2022) The Role of Catecholamines in Pathophysiological Liver Processes. Cells, 11, Article 1021. [Google Scholar] [CrossRef] [PubMed]
[10] Tanimizu, N., Ichinohe, N. and Mitaka, T. (2023) β-Adrenergic Receptor Agonist Promotes Ductular Expansion during 3, 5-Diethoxycarbonyl-1, 4-Dihydrocollidine-Induced Chronic Liver Injury. Scientific Reports, 13, Article No. 7084. [Google Scholar] [CrossRef] [PubMed]
[11] Tanaka, M., Jeong, J., Thomas, C., et al. (2023) The Sympathetic Nervous System Promotes Hepatic Lymphangiogenesis, Which Is Protective Against Liver Fibrosis. The American Journal of Pathology, 193, 2182-2202. [Google Scholar] [CrossRef] [PubMed]
[12] Wilde, A.B., Greverath, L.M., Steinhagen, L.M., et al. (2022) Evaluation of Inhibitory Antibodies against the Muscarinic Acetylcholine Receptor Type 3 in Patients with Primary Biliary Cholangitis and Primary Sclerosing Cholangitis. Journal of Clinical Medicine, 11, Article 681. [Google Scholar] [CrossRef] [PubMed]
[13] Yeo, X.Y., Tan, L.Y., Chae, W.R., et al. (2023) Liver’s Influence on the Brain through the Action of Bile Acids. Frontiers in Neuroscience, 17, Article 1123967. [Google Scholar] [CrossRef] [PubMed]
[14] Ren, W., Hua, M., Cao, F., et al. (2024) The Sympathetic-Immune Milieu in Metabolic Health and Diseases: Insights from Pancreas, Liver, Intestine, and Adipose Tissues. Advanced Science, 11, e2306128. [Google Scholar] [CrossRef] [PubMed]
[15] Kanno, N., LeSage, G., Glaser, S., et al. (2001) Regulation of Cholangiocyte Bicarbonate Secretion. American Journal of Physiology Gastrointestinal and Liver Physiology, 281, G612-G625. [Google Scholar] [CrossRef
[16] Barke, R.A., Brady, P.S. and Brady, L.J. (1993) The Regulation of Mitochondrial Fatty Acid Oxidation and Hepatic Gene Expression by Catecholamine. The Journal of Surgical Research, 54, 95-101. [Google Scholar] [CrossRef] [PubMed]
[17] Li, X. and Wang, H. (2020) Multiple Organs Involved in the Pathogenesis of Non-Alcoholic Fatty Liver Disease. Cell & Bioscience, 10, Article No. 140. [Google Scholar] [CrossRef] [PubMed]
[18] Lin, E.E., Scott-Solomon, E. and Kuruvilla, R. (2021) Peripheral Innervation in the Regulation of Glucose Homeostasis. Trends in Neurosciences, 44, 189-202. [Google Scholar] [CrossRef] [PubMed]
[19] Huang, Y., He, Z., Manyande, A., et al. (2022) Nerve Regeneration in Transplanted Organs and Tracer Imaging Studies: A Review. Frontiers in Bioengineering and Biotechnology, 10, Article 966138. [Google Scholar] [CrossRef] [PubMed]
[20] Scherer, T., Sakamoto, K. and Buettner, C. (2021) Brain Insulin Signalling in Metabolic Homeostasis and Disease. Nature Reviews Endocrinology, 17, 468-483. [Google Scholar] [CrossRef] [PubMed]
[21] Mirzadeh, Z., Faber, C.L. and Schwartz, M.W. (2022) Central Nervous System Control of Glucose Homeostasis: A Therapeutic Target for Type 2 Diabetes? Annual Review of Pharmacology and Toxicology, 62, 55-84. [Google Scholar] [CrossRef] [PubMed]
[22] Lechner, S.G., Markworth, S., Poole, K., et al. (2011) The Molecular and Cellular Identity of Peripheral Osmoreceptors. Neuron, 69, 332-344. [Google Scholar] [CrossRef] [PubMed]
[23] Häussinger, D. (2004) Neural Control of Hepatic Osmolytes and Parenchymal Cell Hydration. The Anatomical Record, 280A, 893-900. [Google Scholar] [CrossRef] [PubMed]
[24] Oyewunmi, O.A., Lei, L.Y., Laurin, J.K.H., et al. (2023) Hemodynamic Effects of the Osmopressor Response: A Systematic Review and Meta-Analysis. Journal of the American Heart Association, 12, e029645. [Google Scholar] [CrossRef
[25] García-Prieto, J., Villena-Gutiérrez, R., Gómez, M., et al. (2017) Neutrophil Stunning by Metoprolol Reduces Infarct Size. Nature Communications, 8, Article No. 14780. [Google Scholar] [CrossRef] [PubMed]
[26] Wong, C.H., Jenne, C.N., Lee, W.Y., et al. (2011) Functional Innervation of Hepatic INKT Cells Is Immunosuppressive Following Stroke. Science, 334, 101-105. [Google Scholar] [CrossRef] [PubMed]
[27] Gu, X., Chu, Q., Ma, X., et al. (2022) New Insights into INKT Cells and Their Roles in Liver Diseases. Frontiers in Immunology, 13, Article 1035950. [Google Scholar] [CrossRef] [PubMed]
[28] Wang, X.Z., Xue, R.F., Zhang, S.Y., et al. (2018) Activation of Natural Killer T Cells Contributes to Triptolide-Induced Liver Injury in Mice. Acta Pharmacologica Sinica, 39, 1847-1854. [Google Scholar] [CrossRef] [PubMed]
[29] Oben, J.A., Roskams, T., Yang, S., et al. (2003) Sympathetic Nervous System Inhibition Increases Hepatic Progenitors and Reduces Liver Injury. Hepatology, 38, 664-673. [Google Scholar] [CrossRef] [PubMed]
[30] Liu, T., Li, J., Li, Q., et al. (2023) Environmental Eustress Promotes Liver Regeneration through the Sympathetic Regulation of Type 1 Innate Lymphoid Cells to Increase IL-22 in Mice. Hepatology, 78, 136-149. [Google Scholar] [CrossRef
[31] Blum, D., Torch, S., Lambeng, N., et al. (2001) Molecular Pathways Involved in the Neurotoxicity of 6-OHDA, Dopamine and MPTP: Contribution to the Apoptotic Theory in Parkinson’s Disease. Progress in Neurobiology, 65, 135-172. [Google Scholar] [CrossRef
[32] Lin, J.C., Peng, Y.J., Wang, S.Y., et al. (2015) Role of the Sympathetic Nervous System in Carbon Tetrachloride-Induced Hepatotoxicity and Systemic Inflammation. PLOS ONE, 10, e0121365. [Google Scholar] [CrossRef] [PubMed]
[33] Medina Pizaño, M.Y., Loera Arias, M.J., Montes De Oca Luna, R., et al. (2023) Neuroimmunomodulation of Adrenoblockers during Liver Cirrhosis: Modulation of Hepatic Stellate Cell Activity. Annals of Medicine, 55, 543-557. [Google Scholar] [CrossRef] [PubMed]
[34] Xue, J., Jiang, T., Humaerhan, J., et al. (2024) Impact of Liver Sympathetic Nervous System on Liver Fibrosis and Regeneration after Bile Duct Ligation in Rats. Journal of Molecular Neuroscience, 74, Article No. 4. [Google Scholar] [CrossRef] [PubMed]
[35] Soeda, J., Mouralidarane, A., Ray, S., et al. (2014) The β-Adrenoceptor Agonist Isoproterenol Rescues Acetaminophen-Injured Livers through Increasing Progenitor Numbers by Wnt in Mice. Hepatology, 60, 1023-1034. [Google Scholar] [CrossRef] [PubMed]
[36] Huan, H.B., Wen, X.D., Chen, X.J., et al. (2017) Sympathetic Nervous System Promotes Hepatocarcinogenesis by Modulating Inflammation through Activation of α1-Adrenergic Receptors of Kupffer Cells. Brain, Behavior, and Immunity, 59, 118-134. [Google Scholar] [CrossRef] [PubMed]
[37] Hurr, C., Simonyan, H., Morgan, D.A., et al. (2019) Liver Sympathetic Denervation Reverses Obesity-Induced Hepatic Steatosis. The Journal of Physiology, 597, 4565-4580. [Google Scholar] [CrossRef
[38] Sigala, B., McKee, C., Soeda, J., et al. (2013) Sympathetic Nervous System Catecholamines and Neuropeptide Y Neurotransmitters Are Upregulated in Human NAFLD and Modulate the Fibrogenic Function of Hepatic Stellate Cells. PLOS ONE, 8, e72928. [Google Scholar] [CrossRef] [PubMed]
[39] Hall, C., Sato, K., Wu, N., et al. (2017) Regulators of Cholangiocyte Proliferation. Gene Expression, 17, 155-171. [Google Scholar] [CrossRef
[40] Satapathy, S.K., Ochani, M., Dancho, M., et al. (2011) Galantamine Alleviates Inflammation and Other Obesity-Asso-ciated Complications in High-Fat Diet-Fed Mice. Molecular Medicine (Cambridge, Mass), 17, 599-606. [Google Scholar] [CrossRef] [PubMed]
[41] Hur, M.H., Song, W., Cheon, D.H., et al. (2023) Chemogenetic Stimulation of the Parasympathetic Nervous System Lowers Hepatic Lipid Accumulation and Inflammation in a Nonalcoholic Steatohepatitis Mouse Model. Life Sciences, 321, Article ID: 121533. [Google Scholar] [CrossRef] [PubMed]
[42] Nishio, T., Taura, K., Iwaisako, K., et al. (2017) Hepatic Vagus Nerve Regulates Kupffer Cell Activation via α7 Nicotinic Acetylcholine Receptor in Nonalcoholic Steatohepatitis. Journal of Gastroenterology, 52, 965-976. [Google Scholar] [CrossRef] [PubMed]
[43] Kimura, K., Tanida, M., Nagata, N., et al. (2016) Central Insulin Action Activates Kupffer Cells by Suppressing Hepatic Vagal Activation via the Nicotinic α 7 Acetylcholine Receptor. Cell Reports, 14, 2362-2374. [Google Scholar] [CrossRef] [PubMed]
[44] Hiramoto, T., Chida, Y., Sonoda, J., et al. (2008) The Hepatic Vagus Nerve Attenuates Fas-Induced Apoptosis in the Mouse Liver via α7 Nicotinic Acetylcholine Receptor. Gastroenterology, 134, 2122-2131. [Google Scholar] [CrossRef] [PubMed]
[45] Li, Y., Xu, Z., Yu, Y., et al. (2014) The Vagus Nerve Attenuates Fulminant Hepatitis by Activating the Src Kinase in Kuppfer Cells. Scandinavian Journal of Immunology, 79, 105-112. [Google Scholar] [CrossRef] [PubMed]
[46] Steinebrunner, N., Mogler, C., Vittas, S., et al. (2014) Pharmacologic Cholinesterase Inhibition Improves Survival in Acetaminophen-Induced Acute Liver Failure in the Mouse. BMC Gastroenterology, 14, Article No. 148. [Google Scholar] [CrossRef
[47] Cassiman, D., Libbrecht, L., Sinelli, N., et al. (2002) The Vagal Nerve Stimulates Activation of the Hepatic Progenitor Cell Compartment via Muscarinic Acetylcholine Receptor Type 3. The American Journal of Pathology, 161, 521-430. [Google Scholar] [CrossRef
[48] Fonseca, R.C., Bassi, G.S., Brito, C.C., et al. (2019) Vagus Nerve Regulates the Phagocytic and Secretory Activity of Resident Macrophages in the Liver. Brain, Behavior, and Immunity, 81, 444-454. [Google Scholar] [CrossRef] [PubMed]
[49] Ikeda, O., Ozaki, M., Murata, S., et al. (2009) Autonomic Regulation of Liver Regeneration after Partial Hepatectomy in Mice. The Journal of Surgical Research, 152, 218-223. [Google Scholar] [CrossRef] [PubMed]
[50] Izumi, T., Imai, J., Yamamoto, J., et al. (2018) Vagus-Macrophage-Hepatocyte Link Promotes Post-Injury Liver Regeneration and Whole-Body Survival through Hepatic FoxM1 Activation. Nature Communications, 9, Article No. 5300. [Google Scholar] [CrossRef] [PubMed]
[51] Amir, M., Yu, M., He, P., et al. (2020) Hepatic Autonomic Nervous System and Neurotrophic Factors Regulate the Pathogenesis and Progression of Non-Alcoholic Fatty Liver Disease. Frontiers in Medicine, 7, Article 62. [Google Scholar] [CrossRef] [PubMed]
[52] Inoue, T., Ito, Y., Nishizawa, N., et al. (2018) RAMP1 in Kupffer Cells Is a Critical Regulator in Immune-Mediated Hepatitis. PLOS ONE, 13, e0200432. [Google Scholar] [CrossRef] [PubMed]
[53] Wan, Y., Meng, F., Wu, N., et al. (2017) Substance P Increases Liver Fibrosis by Differential Changes in Senescence of Cholangiocytes and Hepatic Stellate Cells. Hepatology, 66, 528-541. [Google Scholar] [CrossRef] [PubMed]
[54] Piao, J., Jeong, J., Jung, J., et al. (2019) Substance P Promotes Liver Sinusoidal Endothelium-Mediated Hepatic Regeneration by NO/HGF Regulation. Journal of Interferon & Cytokine Research, 39, 147-154. [Google Scholar] [CrossRef] [PubMed]
[55] Ko, H., Kim, Y.I. and Ahn, H.J. (2022) Effects of Substance P for Liver Regeneration in Rat Hepatectomy Models: A Preliminary Experimental Animal Study. Annals of Transplantation, 27, e934801. [Google Scholar] [CrossRef
[56] Kim, S. and Hong, H.S. (2021) Substance-P Prevents the Cholestatic Liver Injury by Regulating Inflammatory Responses. Peptides, 137, Article ID: 170494. [Google Scholar] [CrossRef] [PubMed]
[57] Mizutani, T., Yokoyama, Y., Kokuryo, T., et al. (2013) Calcitonin Gene-Related Peptide Regulates the Early Phase of Liver Regeneration. The Journal of Surgical Research, 183, 138-145. [Google Scholar] [CrossRef] [PubMed]
[58] Laschinger, M., Wang, Y., Holzmann, G., et al. (2020) The CGRP Receptor Component RAMP1 Links Sensory Innervation with YAP Activity in the Regenerating Liver. FASEB Journal, 34, 8125-8138. [Google Scholar] [CrossRef