| 摘要: |
| 目的：基于网络药理学方法和分子对接技术探讨当归治疗2型糖尿病感音神经性听力损失的作用机制。方法：通过中药分子机制的生物信息学注释数据库平台筛选当归的活性成分及靶点，借助人类基因数据库和人类孟德尔遗传数据库检索疾病相关靶点。运用韦恩在线分析工具对药物靶点与疾病靶点比对，获得交集靶标。运用蛋白质相互作用数据库构建蛋白质-蛋白质相互作用(protein-protein interaction，PPI)网络，筛选关键靶点，并对关键靶点进行基因本体(gene ontology，GO)功能与京都基因和基因组数据库(Kyoto Encyclopedia of Genes and Genomes，KEGG)通路富集分析。利用Cytoscape构建中药当归的调控网络;运用AutoDock软件对关键靶点与活性成分的结合能力进行验证分析。结果：当归含64种活性成分，涉及716个作用靶点，其中342个靶点与2型糖尿病感音神经性听力损失疾病靶点存在交集，核心靶点有信号传导及转录激活蛋白3（signal transducer and activator of transcription 3，STAT3）、肿瘤蛋白（tumor protein 53，TP53）、丝氨酸/苏氨酸蛋白激酶（serine/threonine-protein kinase，AKT1）、白细胞介素-6(interleukin-6，IL-6)、Jun原癌基因(Jun Proto-Oncogene，JUN)。KEGG通路富集分析结果显示，磷脂酰肌醇3激酶/蛋白激酶B（phosphatidylinositol 3-kinase-Protein Kinase B，PI3K-Akt）、脂质与动脉粥样硬化通路 （lipid and atherosclerosis）、高级糖基化终产物/受体(advanced glycation end products/ receptor for advanced glycation end products，AGE/RAGE)、白细胞介素-17(interleukin-17，IL-17)、肿瘤坏死因子(tumor necrosis factor，TNF）信号通路为关键通路。当归治疗2型糖尿病感音神经性听力损失的核心活性成分为姜黄素、维生素D3、柚皮素。分子对接验证结果显示，姜黄素、维生素D3、柚皮素与靶点有良好的结合能力。结论：当归可能通过PI3K-Akt、Lipid and atherosclerosis、AGE/RAGE、IL-17、TNF通路，影响炎症和氧化应激，缓解内耳细胞损伤。 |
| 关键词: 2型糖尿病感音神经性听力损失 当归 网络药理学 分子对接 作用机制 |
| DOI： |
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| Mechanism of action of Angelica sinensis in treatment of sensorineural hearing loss in type 2 diabetes:A study based on network pharmacology |
| ZHANG Peipei,GAO Xinran,LI Qinwei |
| (School of Pharmacy，Heze University，Heze 274000，Shandong，China;Department of Otorhinolaryngology，Heze Municipal Hospital，Heze 274000，Shandong，China) |
| Abstract: |
| Objective：To investigate the mechanism of action of Angelica sinensis in the treatment of sensorineural hearing loss in type 2 diabetes based on network pharmacology and molecular docking.Methods：The Bioinformatics Annotation Database for Molecular Mechanism of Traditional Chinese Medicine was used to obtain the active components and targets of Angelica sinensis，and human gene database and Online Mendelian Inheritance in Man database were used to obtain disease-related targets.The online Venn analysis tool was used to compare the drug targets with the disease targets and obtain the intersecting targets.The Protein-Protein Interaction Database was used to construct a protein-protein interaction network and identify the key targets，and the gene ontology functional enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed for these key genes.Cytoscape was used to construct a regulatory network of Angelica sinensis，and AutoDock software was used to analyze the binding capacity between key targets and active components.Results：There were 64 active components in Angelica sinensis，involving 716 action targets，among which 342 targets intersected with the disease targets of sensorineural hearing loss in type 2 diabetes，and the core targets included signal transducer and activator of transcription 3，tumor protein 53，serine/threonine-protein kinase，interleukin-6，and Jun.The KEGG pathway enrichment analysis showed that the key pathways included the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway，the lipid and atherosclerosis signaling pathway，the advanced glycation end products/receptor for advanced glycation end products (AGE/RAGE) signaling pathway，the interleukin-17 (IL-17) signaling pathway，and the tumor necrosis factor (TNF) signaling pathway.Curcumin，vitamin D3，and naringenin were the core active components of Angelica sinensis in the treatment of sensorineural hearing loss in type 2 diabetes.Molecular docking showed that curcumin，vitamin D3，and naringenin had good binding ability to targets.Conclusion：Angelica sinensis may affect inflammation and oxidative stress and alleviate inner ear cell damage through the PI3K/Akt signaling pathway，the lipid and atherosclerosis signaling pathway，the AGE/RAGE signaling pathway，the IL-17 signaling pathway，and the TNF signaling pathway. |
| Key words: sensorineural hearing loss in type 2 diabetes Angelica sinensis network pharmacology molecular docking mechanism of action |
