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基于网络药理学探讨李氏接骨散对骨折的作用机制
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Abstract:
目的：基于网络药理学方法预测李氏接骨散治疗骨折的作用机制，并通过动物实验进行验证。方法：通过中药系统药理学数据库分析平台(TCMSP)、文献报道以及Swiss Target Prediction筛选李氏接骨散主要活性成分及靶点，利用GeneCards数据库收集骨折靶点，再使用String数据库和Cystoscope 3.7.2软件构建蛋白相互作用(PPI)网络，同时筛选核心靶点，建立“李氏接骨散–活性成分–骨折–靶点”网络，并对潜在核心靶点进行基因本体(geneontology, GO)功能富集分析和京都基因与基因组百科全书(Kyoto encyclopedia of genes and genomes, KEGG)通路富集分析。最后通过动物实验对李氏接骨散治疗骨折进行疗效分析，对部分靶点进行验证。结果：共筛选获得李氏接骨散活性成分20个及其相应靶点514个，骨折靶点5264个，两者交集靶点306个。李氏接骨散治疗骨折潜在核心靶点包括肿瘤蛋白p53 (TP53)、丝氨酸/苏氨酸蛋白激酶AKT (AKT1)、激活蛋白1 (JUN)、白介素6 (IL6)、表皮生长因子受体(EGFR)、肿瘤坏死因子(TNF)等。通路富集分析中与李氏接骨散治疗骨折密切相关的通路主要涉及癌症中的通路(Pathways in cancer)、血脂与动脉粥样硬化(Lipid and atherosclerosis)、化学致癌作用－受体活化(Chemical carcinogenesis-receptor activation)、糖尿病并发症中的AGE-RAGE信号通路(AGE-RAGE signaling pathway in diabetic complications)、MAPK信号通路(MAPK signaling pathway)、小细胞肺癌(Small cell lung cancer)。结论：该研究以网络药理学分析李氏接骨散治疗骨折的作用机制，为李氏接骨散在临床治疗骨折研究提供了初步依据。
Objective: This study explores the mechanism of Li’s Jiegu San in treating fractures using network pharmacology validated by animal experiments. Methods: The research identified the main active components and targets of Li’s Jiegu San through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), literature reports, and Swiss Target Prediction. Fracture-related targets were collected from the GeneCards database. Using the String database and Cytoscape 3.7.2 software, we constructed a protein-protein interaction (PPI) network and identified core targets. The study then established a “Li’s Jiegu San-Active Components-Fracture-Targets” network, performing Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on the potential core targets. Animal experiments further assessed the therapeutic effects of Li’s Jiegu San on fractures with validation of specific targets. Results: The study identified 20 active components of Li’s Jiegu San and 514 corresponding targets. Additionally, 5264 fracture-related targets were collected, with 306 overlapping targets. The core targets for Li’s Jiegu San in treating fractures include tumor protein p53 (TP53), serine/threonine protein kinase AKT (AKT1), activator protein 1 (JUN), interleukin 6 (IL6), epidermal growth factor receptor (EGFR), and tumor necrosis factor (TNF). Pathway enrichment analysis highlighted pathways in cancer, lipid and atherosclerosis, chemical carcinogenesis-receptor
| [1] | 曹立梅. 风险护理在女性脊柱骨折患者围手术期护理中的应用[J]. 妇儿健康导刊, 2024, 3(14): 113-116. |
| [2] | Ru, J., Li, P., Wang, J., Zhou, W., Li, B., Huang, C., et al. (2014) TCMSP: A Database of Systems Pharmacology for Drug Discovery from Herbal Medicines. Journal of Cheminformatics, 6, Article No. 13. https://doi.org/10.1186/1758-2946-6-13 |
| [3] | Kong, X., Liu, C., Zhang, Z., Cheng, M., Mei, Z., Li, X., et al. (2023) BATMAN-TCM 2.0: An Enhanced Integrative Database for Known and Predicted Interactions between Traditional Chinese Medicine Ingredients and Target Proteins. Nucleic Acids Research, 52, D1110-D1120. https://doi.org/10.1093/nar/gkad926 |
| [4] | Xu, X., Zhang, W., Huang, C., Li, Y., Yu, H., Wang, Y., et al. (2012) A Novel Chemometric Method for the Prediction of Human Oral Bioavailability. International Journal of Molecular Sciences, 13, 6964-6982. https://doi.org/10.3390/ijms13066964 |
| [5] | 孔庆雅. 类药性质研究: 药物关键理化性质和结构的统计与分析[D]: [硕士学位论文]. 上海: 华东理工大学, 2015. |
| [6] | Bateman, A., Martin, M.-J., Orchard, S., et al. (2023) UniProt: The Universal Protein Knowledgebase in 2023. Nucleic Acids Research, 51, D523-D531. |
| [7] | Rappaport, N., Fishilevich, S., Nudel, R., Twik, M., Belinky, F., Plaschkes, I., et al. (2017) Rational Confederation of Genes and Diseases: NGS Interpretation via Genecards, Malacards and Varelect. BioMedical Engineering Online, 16, Article No. 72. https://doi.org/10.1186/s12938-017-0359-2 |
| [8] | Piñero, J., Ramírez-Anguita, J.M., Saüch-Pitarch, J., Ronzano, F., Centeno, E., Sanz, F., et al. (2019) The Disgenet Knowledge Platform for Disease Genomics: 2019 Update. Nucleic Acids Research, 48, D845-D855. https://doi.org/10.1093/nar/gkz1021 |
| [9] | Amberger, J.S., Bocchini, C.A., Scott, A.F. and Hamosh, A. (2018) Omim.org: Leveraging Knowledge across Phenotype-Gene Relationships. Nucleic Acids Research, 47, D1038-D1043. https://doi.org/10.1093/nar/gky1151 |
| [10] | Sharma, S., Ciufo, S., Starchenko, E., Darji, D., Chlumsky, L., Karsch-Mizrachi, I., et al. (2019) The NCBI Biocollections Database. Database, 2019, baz057. https://doi.org/10.1093/database/baz057 |
| [11] | Szklarczyk, D., Gable, A.L., Nastou, K.C., Lyon, D., Kirsch, R., Pyysalo, S., et al. (2020) The STRING Database in 2021: Customizable Protein-Protein Networks, and Functional Characterization of User-Uploaded Gene/Measurement Sets. Nucleic Acids Research, 49, D605-D612. https://doi.org/10.1093/nar/gkaa1074 |
| [12] | Lotia, S., Montojo, J., Dong, Y., Bader, G.D. and Pico, A.R. (2013) Cytoscape App Store. Bioinformatics, 29, 1350-1351. https://doi.org/10.1093/bioinformatics/btt138 |
| [13] | Shannon, P., Markiel, A., Ozier, O., Baliga, N.S., Wang, J.T., Ramage, D., et al. (2003) Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks. Genome Research, 13, 2498-2504. https://doi.org/10.1101/gr.1239303 |
| [14] | Zhou, Y., Zhou, B., Pache, L., Chang, M., Khodabakhshi, A.H., Tanaseichuk, O., et al. (2019) Metascape Provides a Biologist-Oriented Resource for the Analysis of Systems-Level Datasets. Nature Communications, 10, Article No. 1523. https://doi.org/10.1038/s41467-019-09234-6 |
| [15] | 张宇. 丝线内固定荷包式缝合治疗髌骨骨折的临床应用[D]: [硕士学位论文]. 哈尔滨: 黑龙江中医药大学, 2009. |
| [16] | Calderon-Montano, J.M., Burgos-Moron, E., Perez-Guerrero, C. and Lopez-Lazaro, M. (2011) A Review on the Dietary Flavonoid Kaempferol. Mini-Reviews in Medicinal Chemistry, 11, 298-344. https://doi.org/10.2174/138955711795305335 |
| [17] | Wang, R., Zeng, M., Zhang, B., Zhang, Q., Jia, J., Cao, B., et al. (2022) β-sitosterol Inhibits Ovalbumin-Induced Asthma-Related Inflammation by Regulating Dendritic Cells. Immunopharmacology and Immunotoxicology, 44, 1013-1021. https://doi.org/10.1080/08923973.2022.2102990 |
| [18] | Hah, Y., Lee, W.K., Lee, S., Kim, E.J., Lee, J.H., Lee, S., et al. (2022) Β-Sitosterol Attenuates Dexamethasone-Induced Muscle Atrophy via Regulating Foxo1-Dependent Signaling in C2C12 Cell and Mice Model. Nutrients, 14, Article 2894. https://doi.org/10.3390/nu14142894 |
| [19] | 姜耘宙, 汪正明, 王瑞, 等. β-谷甾醇改善绝经后骨质疏松的实验研究[J]. 浙江中医药大学学报, 2024, 48(2): 131-137+146. |
| [20] | 汤胜尧, 胡珉华, 周若愚, 等. 木犀草素对骨缺损成骨修复的作用及机制研究[J]. 中国药房, 2023, 34(7): 807-813. |
| [21] | 王知刚, 胡聪, 张波. 木犀草素调控OPG对牙周炎大鼠干预效果及作用机制[J]. 中国老年学杂志, 2023, 43(24): 6025-6028. |
| [22] | 周志远, 卢群, 刘洋, 等. 豆甾醇的研究及开发进展[J]. 中国当代医药, 2015, 22(24): 15-17. |
