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论著.生物信息技术 | 更新时间:2023-09-21
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基于网络药理学和分子对接技术探讨 解痉散瘀汤治疗肩袖损伤的作用机制
Mechanism of Jiejing Sanyu Decoction for the treatment of rotator cuff tear: an exploration based on network pharmacology and molecular docking technique

广西医学 2023第45卷14期 页码:1711-1717

作者机构:林泽宏,在读硕士研究生,研究方向:脊柱与四肢退行性疾病的中医治疗。

基金信息:广西研究生教育创新计划项目(YCSY2022011);广西中医药大学桂派中医药传承创新团队项目(2022V001)

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目的运用网络药理学和分子对接技术探讨解痉散瘀汤治疗肩袖损伤的作用机制。方法(1)通过中药系统药理学数据库和分析平台(TCMSP)、SwissADME平台筛选解痉散瘀汤10种中药的主要活性成分,再通过TCMSP和 SwissTargetPrediction平台筛选主要活性成分的作用靶点。通过GeneCards数据库和OMIM数据库获取肩袖损伤的相关靶点,再将其与主要活性成分的作用靶点取交集,得到解痉散瘀汤治疗肩袖损伤的潜在作用靶点。(2)使用Cytoscape 3.9.1软件构建成分-靶点网络,筛选解痉散瘀汤治疗肩袖损伤的关键活性成分。通过STRING 11.5平台和Cytoscape 3.9.1软件构建潜在作用靶点的蛋白-蛋白相互作用网络,筛选解痉散瘀汤治疗肩袖损伤的核心靶点。(3)使用DAVID数据库对潜在作用靶点进行基因本体论(GO)功能富集分析及京都基因和基因组百科全书(KEGG)通路富集分析。(4)通过AutoDock 1.5.6软件进行关键活性成分与核心靶点蛋白的分子对接。结果(1)共获得解痉散瘀汤主要活性成分作用靶点835个,肩袖损伤相关靶点357个,取交集后获得95个潜在作用靶点。(2)共获得5个关键活性成分和5个核心靶点,前者包括槲皮素、环(L-脯氨酸-L-苯丙氨酸)二肽、木犀草素、L-脯氨酰-L-亮氨酰-L-亮氨酰甘氨酸、山柰酚,后者包括白细胞介素(IL)-1B、丝氨酸/苏氨酸激酶1(AKT1)、血管内皮生长因子 A(VEGFA)、基质金属蛋白酶9(MMP9)、纤维连接蛋白1(FN1)。(3)GO功能富集分析结果显示,潜在作用靶点涉及的生物过程主要有脂多糖反应、低氧反应、过氧化氢反应、胶原分解代谢过程、蛋白水解等;KEGG通路富集分析结果显示,潜在作用靶点主要涉及晚期糖基化终末产物-晚期糖基化终末产物受体信号通路、缺氧诱导因子1信号通路、肿瘤坏死因子信号通路、IL-17信号通路等。(4)分子对接结果显示所有关键活性成分与核心靶点蛋白均有良好的结合活性。结论解痉散瘀汤的多个活性成分可能通过作用于IL-1B、AKT1、VEGFA、MMP9、FN1等靶点,来影响与炎症反应、细胞凋亡及血管生成相关的信号通路,从而抑制炎症反应、调控损伤组织局部细胞凋亡、抑制组织过度重塑,进而发挥治疗肩袖损伤的作用。
ObjectiveTo explore the mechanism of Jiejing Sanyu Decoction for the treatment of rotator cuff tear by utilizing network pharmacology and molecular docking technique. Methods(1) The main active components of 10 Traditional Chinese Medicines in Jiejing Sanyu Decoction were screened through the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and SwissADME platform, and then the effect targets of main active components were screened through the TCMSP and SwissTargetPrediction platform. Targets related to rotator cuff tear were obtained by GeneCards and OMIM databases, and then was intersected with the effect targets of main active components for acquiring potential effect targets of Jiejing Sanyu Decoction for treating rotator cuff tear. (2) The component-target network was established by using the Cytoscape 3.9.1 software for screening the key active components of Jiejing Sanyu Decoction for treating rotator cuff tear. The protein-protein interaction network of potential effect targets was established for screening core targets of Jiejing Sanyu Decoction for treating rotator cuff tear through the STRING 11.5 platform and Cytoscape 3.9.1 software. (3) The Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were conducted on potential effect targets by employing DAVID database. (4) The AutoDock 1.5.6 software was used to perform molecular docking between key active components and proteins of the core targets. Results(1) A total of 835 effect targets of main active components of Jiejing Sanyu Decoction, 357 targets related to rotator cuff tear were obtained, and 95 potential effect targets were acquired after intersection. (2) A total of 5 key active components and 5 core targets were obtained, the former contained quercetin, cyclo (L-phe-L-pro), luteolin, L-prolyl-L-leucyl-L-leucylglycine, and kaempferol, and the latter included interleukin (IL)-1B, serine/threonine kinase 1 (AKT1), vascular endothelial growth factor A (VEGFA), matrix metalloproteinase 9 (MMP9), and fibronectin 1 (FN1). (3) The results of GO functional enrichment analysis revealed that the biological processes involved in potential effect targets were mainly response to lipopolysaccharide, response to hypoxia, response to hydrogen peroxide, collagen catabolic process, proteolysis, etc.; in addition, the results of KEGG pathway enrichment analysis revealed that the potential targets are mainly involved in advanced glycation end products and receptor of advanced glycation end products signaling pathway, hypoxia-inducible factor 1 signaling pathway, tumor necrosis factor signaling pathway, IL-17 signaling pathway, etc. (4) The results of molecular docking depicted that all the key active components exerted good binding activities with the core target proteins. ConclusionMultiple active components of Jiejing Sanyu Decoction may affect signaling pathways related to inflammatory responses, cell apoptosis, and angiogenesis, and further inhibit inflammatory responses, regulate local cell apoptosis in traumatic tissues, inhibit tissue excessive remodeling, so as to exert effects for treating rotator cuff tear through acting on IL-1B, AKT1, VEGFA, MMP9, FN1, and other targets.

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