|
|
基于生物信息学、网络拓扑策略探究针刺干预帕金森病的中枢机制
|
Abstract:
目的：运用文本挖掘、生物信息学、网络拓扑学等方法，探究针刺治疗帕金森病(PD)的多靶点中枢机制。方法：检索文献发现针刺后产生的活性化合物，通过STITCH和SwissTargetPrediction数据库预测潜在作用靶点。利用人类基因数据库、在线人类孟德尔遗传数据库和全球蛋白资源数据库筛选出PD相关的疾病基因靶点。运用Cytoscape3.10.1软件构建共有靶点蛋白质–蛋白质互作网络图，通过DAVID数据库对共有靶点分别进行基因本体富集分析和京都基因组百科全书富集分析并可视化。结果：共鉴定了114个与针刺治疗帕金森病相关的基因靶点，筛选了65条通路。结论：针刺治疗PD与刺激多巴胺分泌，减少多巴胺能神经元凋亡、调节5-羟色胺代谢水平、提高去甲肾上腺素水平、刺激神经营养因子、缓解炎症反应等密切相关。
Objective: To investigate the multi-target mechanism of acupuncture for Parkinson’s disease (PD) using text mining, bioinformatics, and network topology. Methods: Literature was searched to dis-cover active compounds produced after acupuncture, and potential targets of action were predicted by STITCH and SwissTargetPrediction databases. PD-associated disease gene targets were screened using the Human Gene Database, the Online Human Mendelian Inheritance Database, and the Glob-al Protein Resources Database. Cytoscape3.10.1 software was used to construct protein-protein in-teraction network maps of shared targets, and gene ontology enrichment analysis and Kyoto Ge-nome Encyclopedia enrichment analysis of shared targets were performed and visualized by DAVID database, respectively. Results: A total of 114 gene targets related to acupuncture for Parkinson’s disease were identified, and 65 pathways were screened. Conclusion: Acupuncture therapy for PD is closely related to stimulating dopamine secretion, reducing apoptosis of dopaminergic neurons, regulating 5-hydroxytryptamine metabolism levels, increasing norepinephrine levels, stimulating neurotrophic factors, and alleviating inflammatory responses.
| [1] | Kaur, K., Gill, J.S., Bansal, P.K., et al. (2017) Neuroinflammation—A Major Cause for Striatal Dopaminergic Degenera-tion in Parkinson’s Disease. Journal of the Neurological Sciences, 381, 308-314.
https://doi.org/10.1016/j.jns.2017.08.3251 |
| [2] | GBD 2015 Neurological Disorders Collaborator Group (2017) Global, Regional, and National Burden of Neurological Disorders during 1990-2015: A Systematic Analysis for the Global Burden of Disease Study 2015. Lancet Neurology, 11, 877-897. https://doi.org/10.1097/01.ogx.0000511935.64476.66 |
| [3] | 张硕, 高健, 姜立刚. 帕金森病患病率及相关因素的流行病学研究现状[J]. 吉林医药学院学报, 2021, 42(6): 437-439. |
| [4] | Yin, L., Xie, Y.Y., Yin, S.Y., et al. (2015) The S-Nitrosylation Status of PCNA Localized in Cytosol Impacts the Apoptotic Pathway in a Parkinson’s Disease Par-adigm. PLOS ONE, 2, e0117546.
https://doi.org/10.1371/journal.pone.0117546 |
| [5] | Antony, P.M.A., Boyd, O., Trefois, C., et al. (2015) Platelet Mitochondrial Membrane Potential in Parkinson’s Disease. Annals of Clinical and Translational Neurology, 2, 67-73. https://doi.org/10.1002/acn3.151 |
| [6] | 岑川, 何建成. 中医药防治帕金森病药物左旋多巴副作用研究进展[J]. 中华中医药学刊, 2009, 27(12): 2530-2532. |
| [7] | Bove, F., Angeloni, B., Sanginario, P., et al. (2023) Neuroplasticity in Levodopa-Induced Dyskinesias: An Overview on Pathophysiology and Therapeutic Targets. Progress in Neurobiology, 232, Article ID: 102548.
https://doi.org/10.1016/j.pneurobio.2023.102548 |
| [8] | Tian, T., Sun, Y., Wu, H., et al. (2016) Acupuncture Pro-motes MTOR-Independent Autophagic Clearance of Aggregation-Prone Proteins in Mouse Brain. Scientific Reports, 6, Article No. 19714. https://doi.org/10.1038/srep19714 |
| [9] | Kwon, M., Cheong, M.J., Leem, J.T. and Kim, T.H.. (2021) Effect of Acupuncture on Movement Function in Patients with Parkinson’s Disease: Network Meta-Analysis of Randomized Controlled Trials. Healthcare, 9, Article 1502.
https://doi.org/10.3390/healthcare9111502 |
| [10] | Pereira, C.R., Criado, M.B., Machado, J., et al. (2021) Acute Ef-fects of Acupuncture in Balance and Gait of Parkinson Disease Patients—A Preliminary Study. Complementary Thera-pies in Clinical Practice, 45, Article ID: 101479.
https://doi.org/10.1016/j.ctcp.2021.101479 |
| [11] | Moon, S., Sarmento, C.V.M., Colgrove, Y. and Liu, W. (2021) Complementary Health Approaches for People with Parkinson Disease. Archives of Physical Medicine and Rehabilitation, 101, 1475-1477.
https://doi.org/10.1016/j.apmr.2020.03.024 |
| [12] | Li, K., Xu, S., Wang, R., et al. (2023) Electroacupuncture for Mo-tor Dysfunction and Constipation in Patients with Parkinson’s Disease: A Randomised Controlled Multi-Centre Trial. EClinicalMedicine, 56, Article ID: 101814.
https://doi.org/10.1016/j.eclinm.2022.101814 |
| [13] | Ning, B., Wang, Z., Wu, Q., et al. (2023) Acupuncture Inhibits Autophagy and Repairs Synapses by Activating the MTOR Pathway in Parkinson’s Disease Depression Model Rats. Brain Research, 1808, Article ID: 148320.
https://doi.org/10.1016/j.brainres.2023.148320 |
| [14] | Yeo, S. and Lim, S. (2019) Acupuncture Inhibits the Increase in Alpha-Synuclein by Modulating SGK1 in an MPTP Induced Parkinsonism Mouse Model. The American Journal of Chinese Medicine, 47, 527-539.
https://doi.org/10.1142/S0192415X19500277 |
| [15] | Khalil, W.K.B., Assaf, N., ElShebiney, S.A. and Salem, N.A. (2015) Neuroprotective Effects of Bee Venom Acupuncture Therapy against Rotenone-Induced Oxidative Stress and Apoptosis. Neurochemistry International, 80, 79-86.
https://doi.org/10.1016/j.neuint.2014.11.008 |
| [16] | Sun, M., Wang, M., Yu, Y., et al. (2016) Electroacupuncture Al-leviates Depressive-Like Symptoms and Modulates BDNF Signaling in 6-Hydroxydopamine Rats. Evidence-Based Complementary and Alternative Medicine, 2016, Article ID: 7842362. https://doi.org/10.1155/2016/7842362 |
| [17] | Pak, M.E., Ahn, S.M., Jung, D.H., et al. (2020) Electroacupuncture Therapy Ameliorates Motor Dysfunction via Brain-Derived Neurotrophic Factor and Glial Cell Line-Derived Neu-rotrophic Factor in a Mouse Model of Parkinson’s Disease. The Journals of Gerontology: Series A, 75, 712-721. https://doi.org/10.1093/gerona/glz256 |
| [18] | Kim, S.N., Doo, A.R., Park, J.Y., et al. (2011) Acupuncture Enhances the Synaptic Dopamine Availability to Improve Motor Function in a Mouse Model of Parkinson’s Disease. PLOS ONE, 11, e27566.
https://doi.org/10.1371/journal.pone.0027566 |
| [19] | Yu, J., Min, D., Bai, Y., et al. (2020) Electroacupuncture Alle-viates Parkinson Disease and Regulates the Expression of Brain-Gut Peptides. Experimental Animals, 69, 448-460. https://doi.org/10.1538/expanim.19-0153 |
| [20] | Kim, S.N., Doo, A.R., Park, J.Y., et al. (2014) Combined Treatment with Acupuncture Reduces Effective Dose and Alleviates Adverse Effect of L-Dopa by Normalizing Parkinson’s Dis-ease-Induced Neurochemical Imbalance. Brain Research, 1544, 33-44. https://doi.org/10.1016/j.brainres.2013.11.028 |
| [21] | Shintani, T. and Klionsky, D.J. (2004) Autophagy in Health and Disease: A Double-Edged Sword. Science, 306, 990-995. https://doi.org/10.1126/science.1099993 |
| [22] | Ye, H., Robak, L.A., Yu, M., et al. (2023) Genetics and Pathogenesis of Parkinson’s Syndrome. Annual Review of Pathology: Mechanisms of Disease, 18, 95-121. https://doi.org/10.1146/annurev-pathmechdis-031521-034145 |
| [23] | Nemade, D., Subramanian, T. and Shivkumar, V. (2021) An Update on Medical and Surgical Treatments of Parkinson’s Disease. Aging and Disease, 12, 1021-1035. https://doi.org/10.14336/AD.2020.1225 |
| [24] | Park, H. and Poo, M.M. (2013) Neurotrophin Regulation of Neural Circuit Development and Function. Nature Reviews Neuroscience, 14, 7-23. https://doi.org/10.1038/nrn3379 |
| [25] | Lu, B. (2003) BDNF and Activity-Dependent Synaptic Modulation. Learning & Memory, 10, 86-98.
https://doi.org/10.1101/lm.54603 |
| [26] | Autry, A.E. and Monteggia, L.M. (2012) Brain-Derived Neurotrophic Factor and Neuropsychiatric Disorders. Pharmacological Reviews, 64, 238-258. https://doi.org/10.1124/pr.111.005108 |
| [27] | Miao, C., Li, X. and Zhang, Y. (2023) Effect of Acupuncture on BDNF Signaling Pathways in Several Nervous System Diseases. Frontiers in Neurology, 14, Article 1248348. https://doi.org/10.3389/fneur.2023.1248348 |
| [28] | 杜靖, 孙作厘, 贾军, 等. 高频电针刺激对帕金森病模型大鼠脑组织中γ-氨基丁酸含量的调节作用[J]. 生理学, 2011, 63(4): 305-310. |
| [29] | 王述菊, 马骏, 王彦春, 等. 电针对帕金森病模型大鼠黑质区C-Jun氨基末端激酶和TNF-α、IFN-γ、IL-1β蛋白表达的影响[J]. 中华中医药学刊, 2017, 35(1): 43-46. |
| [30] | Bruno, F., Abondio, P., Montesanto, A., et al. (2023) The Nerve Growth Factor Receptor (NGFR/P75(NTR)): A Major Player in Alzheimer’s Disease. International Journal of Molecular Sciences, 24, Article 3200.
https://doi.org/10.20944/preprints202301.0239.v1 |
| [31] | Bruno, F., Malvaso, A., Canterini, S. and Bruni, A.C. (2022) Antimicrobial Peptides (AMPs) in the Pathogenesis of Alzheimer’s Disease: Implications for Diagnosis and Treatment. Antibiotics, 11, Article 726.
https://doi.org/10.20944/preprints202205.0166.v1 |
| [32] | Shu, Y.H., Lu, X.M., Wei, J.X., et al. (2015) Update on the Role of P75NTR in Neurological Disorders: A Novel Therapeutic Target. Biomedicine & Pharmacotherapy, 76, 17-23. https://doi.org/10.1016/j.biopha.2015.10.010 |
| [33] | Ibá？ez, C.F. and Simi, A. (2012) P75 Neurotrophin Receptor Signaling in Nervous System Injury and Degeneration: Paradox and Opportunity. Trends in Neurosciences, 35, 431-440. https://doi.org/10.1016/j.tins.2012.03.007 |
| [34] | Wang, Q., Wang, H., Meng, W., et al. (2023) The NONRATT023402.2/Rno-MiR-3065-5p/NGFR Axis Affects Levodopa-Induced Dyskinesia in a Rat Model of Parkin-son’s Disease. Cell Death Discovery, 9, Article No. 342.
https://doi.org/10.1038/s41420-023-01644-2 |
| [35] | Signorile, A., Ferretta, A., Pacelli, C., et al. (2023) Resveratrol Treatment in Human Parkin-Mutant Fibroblasts Modulates CAMP and Calcium Homeostasis Regulating the Expression of Mitochondria-Associated Membranes Resident Proteins. Biomolecules, 11, Article 1511. |
| [36] | Li, J., Li, Q., Xie, C., et al. (2004) β-Actin Is Required for Mitochondria Clustering and ROS Generation in TNF-Induced, Caspase-Independent Cell Death. Journal of Cell Science, 117, 4673-4680.
https://doi.org/10.1242/jcs.01339 |
| [37] | Hartmann, A., Hunot, S., Michel, P.P., et al. (2000) Caspase-3: A Vulnera-bility Factor and Final Effector in Apoptotic Death of Dopaminergic Neurons in Parkinson’s Disease. Proceedings of the National Academy of Sciences of the United States of America, 6, 2875-2880. https://doi.org/10.1073/pnas.040556597 |
| [38] | Viswanath, V., Wu, Y., Boonplueang, R., et al. (2001) Caspase-9 Activation Results in Downstream Caspase-8 Activation and Bid Cleavage in 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Induced Parkinson’s Disease. Journal of Neuroscience, 21, 9519-9528. https://doi.org/10.1523/JNEUROSCI.21-24-09519.2001 |
| [39] | 姜勇. MAPK信号转导通路对炎症反应的调控[J]. 生理学报, 2000, 52(4): 267-271, 280. |
| [40] | Xia, X., Harding, T., Weller, M., et al. (2001) Gene Transfer of the JNK Interacting Protein-1 Protects Dopaminergic Neurons in the MPTP Model of Parkinson’s Disease. Proceedings of the National Academy of Sciences of the United States of America, 98, 10433-10438. https://doi.org/10.1073/pnas.181182298 |
| [41] | Wang, W., Ma, C., Mao, Z. and Li, M. (2004) JNK Inhibition as a Potential Strategy in Treating Parkinson’s Disease. Drug News & Perspectives, 17, 646-654. https://doi.org/10.1358/dnp.2004.17.10.873916 |
| [42] | 张万萍, 余永游. 单胺氧化酶抑制药物神经保护作用的研究进展[J]. 山东化工, 2015, 44(1): 62-64. |
| [43] | Finberg, J.P.M. (2019) Inhibitors of MAO-B and COMT: Their Ef-fects on Brain Dopamine Levels and Uses in Parkinson’s Disease. Journal of Neural Transmission, 126, 433-448. https://doi.org/10.1007/s00702-018-1952-7 |
