摘要
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 activation, AGE-RAGE signaling pathway in diabetic complications, MAPK signaling pathway, and small cell lung cancer as closely related to the therapeutic effects of Li’s Jiegu San on fractures. Conclusion: This study provides a preliminary basis for understanding the mechanism of Li’s Jiegu San in treating fractures through network pharmacology analysis offering valuable insights for its clinical application.
出处
《中医学》
2024年第9期2170-2178,共9页
Traditional Chinese Medicine
