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通过网络药理学、分子对接和转录组学研究石蒜碱对甲状腺相关性眼病眼眶成纤维细胞纤维化和炎症的影响。

Investigating the effects of dendrobine on fibrosis and inflammation in orbital fibroblasts of thyroid-associated ophthalmopathy via network pharmacology, molecular docking, and transcriptomics.

作者信息

Xie Meng, Wang Bowen, Chen Jin, Wang Yiyan, Rong Yan, Su Zixuan, Jiang Fagang, Wang Xinghua

机构信息

Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China; Department of Ophthalmology, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, Guizhou Province, China.

Department of Ophthalmology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei Province, China.

出版信息

Eur J Pharmacol. 2025 Sep 5;1002:177871. doi: 10.1016/j.ejphar.2025.177871. Epub 2025 Jun 21.

DOI:10.1016/j.ejphar.2025.177871
PMID:40544935
Abstract

This study aims to evaluate the effects and mechanisms of dendrobine against thyroid-associated ophthalmopathy (TAO). Potential targets of dendrobine and TAO were selected to construct a protein-protein interaction network, elucidating the potential mechanisms of dendrobine against TAO. The potential mechanisms systematically were verified by molecular docking, transcriptomics and in vitro experiments. Orbital fibroblasts (OFs) were isolated from orbital decompression-derived fat tissue, and the effects of dendrobine were studied in transforming growth factor-beta 1 (TGF-β1)-induced fibrosis models and interleukin-1β (IL-1β)-induced inflammation models. The results showed that dendrobine inhibited the migration, fibrosis and levels of inflammatory factors in TAO OFs. Network pharmacology and transcriptomics studies revealed the mechanisms of dendrobine, while in vitro experiments confirmed it alleviates TGF-β1-induced fibrosis in TAO OFs by inhibiting AKT phosphorylation.

摘要

本研究旨在评估石蒜碱对甲状腺相关性眼病(TAO)的作用及机制。选择石蒜碱和TAO的潜在靶点构建蛋白质-蛋白质相互作用网络,阐明石蒜碱对TAO的潜在作用机制。通过分子对接、转录组学和体外实验系统验证潜在机制。从眼眶减压获取的脂肪组织中分离出眼眶成纤维细胞(OFs),并在转化生长因子-β1(TGF-β1)诱导的纤维化模型和白细胞介素-1β(IL-1β)诱导的炎症模型中研究石蒜碱的作用。结果表明,石蒜碱可抑制TAO OFs的迁移、纤维化及炎症因子水平。网络药理学和转录组学研究揭示了石蒜碱的作用机制,而体外实验证实其通过抑制AKT磷酸化减轻TAO OFs中TGF-β1诱导的纤维化。

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