独活寄生汤治疗骨坏死分子机制的网络药理学分析  

Network pharmacological analysis of the molecular mechanism of Duhuo Jisheng(Angelicae pubescentis and loranhti)decoction in the treatment of osteonecrosis and the implications for the treatment of dysbaric osteonecrosis

作　　者：敬梅 吴江红 王少康 王岩 景华 潘颖超 田露露 徐佳丽 方以群 Jing Mei;Wu Jianghong;Wang Shaokang;Wang Yan;Jing Hua;Pan Yingchao;Tian Lulu;Xu Jiali;FangYiqun(Department of Emergency,Naval Medical Center,Naval Medical University,Shanghai 200052,China;Department of Orthopedics,Changhai Hospital,Naval Medical University,Shanghai 200433,China;Department of Emergency,Changhai Hospital,Naval Medical University,Shanghai 200433,China)

机构地区：[1]海军军医大学海军特色医学中心急诊科,上海200052 [2]海军军医大学长海医院创伤骨科,上海200433 [3]海军军医大学长海医院急诊科,上海200433

出　　处：《中华航海医学与高气压医学杂志》2022年第6期762-767,798,共7页Chinese Journal of Nautical Medicine and Hyperbaric Medicine

基　　金：上海市综合医院中西医结合专项(ZHYY-ZXYJHZX-202119)。

摘　　要：目的:运用网络药理学的方法筛选独活寄生汤的主要活性化合物,预测其有效成分治疗骨坏死的相关靶点和可能机制,从而为减压性骨坏死的治疗提供启示。方法:在中医药系统药理学平台中检索和筛选独活寄生汤的活性化合物和作用靶点,同时在疾病基因数据库中检索和筛选骨坏死相关的靶点;运用软件构建“药物-成分-靶点”网络图和“方药-疾病”韦恩图,得到独活寄生汤和骨坏死的交集靶点;然后构建蛋白质互作网络并进行基因本体(GO)功能注释和京都基因与基因组百科全书(KEGG)通路富集分析。结果:共筛选226个活性化合物、271个潜在靶点和468个骨坏死疾病靶点,共得到“方药-疾病”交集靶点61个,其中核心靶点包括血管内皮生长因子A(VEGFA)、白细胞介素-β(IL-1β)、肿瘤坏死因子-α(TNF-α)、白蛋白(ALB)、白细胞介素-6(IL-6)等,主要富集于细胞死亡的正调控等生物过程和低氧诱导因子-1(HIF-1)、核因子-κB(NF-κB)等信号通路上。结论:独活寄生汤可能是通过调节HIF-1、NF-κB等信号通路中的VEGFA、IL-1β、TNF-α、ALB、IL-6等靶点来抑制炎症反应,促进血管生成和成骨细胞增殖等,从而治疗骨坏死,这为减压性骨坏死的治疗提供了启示。Objective:To screen the main active compounds of Duhuo Jisheng(Angelicae pubescentis and loranhti)Decoction by means of network pharmacology,to predict relevant targets and possible mechanisms of these active compounds in the treatment of osteonecrosis,and to provide reference for possible treatments for dysbaric osteonecrosis.Methods:We searched and screened the active compounds and targets of Duhuo Jisheng Decoction on the Traditional Chinese Medicine Systems Pharmacology Database,and identified the targets related to osteonecrosis in the disease gene databases.We used software to construct the network of"ingredient-compound-target"and the Venn diagram of"ingredient-disease",and obtain the intersection targets of Duhuo Jisheng Decoction and osteonecrosis.Then the protein-protein interaction network was constructed and Gene Ontology(GO)functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed.Results:A total of 226 active compounds,271 potential targets,and 468 osteonecrosis-related targets were screened.A total of 61"ingredient-disease"intersection targets were obtained,among which the core targets included VEGFA,IL1B,TNF,ALB,IL6,mainly enriched in the biological processes such as positive regulation of cell death and the signaling pathways of HIF-1 and NF-κB.Conclusion:Duhuo Jisheng Decoction may treat osteonecrosis by regulating VEGFA,IL1B,TNF,ALB,IL6,and other targets through HIF-1,NF-κB,and other signaling pathways to inhibit inflammation,promote angiogenesis,and osteoblast proliferation,hence a possible treatment of dysbaric osteonecrosis.

关 键 词：网络药理学 独活寄生汤 减压性骨坏死 靶点预测 

分 类 号：R285[医药卫生—中药学]