目的 探究依达拉奉对脂多糖激活的BV2小胶质细胞中TDP-43/cGAS/STING信号的影响。 方法 SwissTargetPrediction、Superpred和TargetNet数据库获取依达拉奉潜在作用靶点，经GeneCards、OMIM和TTD数据库筛选出神经炎症相关基因，获得两者交集靶点；用STRING数据库和Cytoscape软件构建蛋白质互作网络；用Metascape数据库进行GO功能富集和KEGG通路富集分析。将BV2小胶质细胞分为对照组、脂多糖激活组和脂多糖加依达拉奉组，采用蛋白质印迹和免疫荧光染色检测TDP-43、cGAS、STING、TNF-α和IL-1β的表达变化。 结果 网络药理学筛选出依达拉奉调节神经炎症的潜在靶点70个，GO共富集1339个条目，KEGG共富集157条信号通路。免疫印迹实验和免疫荧光染色显示，激活的BV2小胶质细胞中TDP-43、cGAS和STING以及炎症因子TNF-α和IL-1β的表达增加，依达拉奉干预后上述因子表达降低。 结论 依达拉奉可抑制BV2细胞中TDP-43/cGAS/STING信号，减轻炎症反应。
Abstract
Objective To explore the effect of Edaravone on TDP-43/cGAS/STING signaling in lipopolysaccharide-activated BV2 microglia. Methods The SwissTargetPrediction, Superpred and TargetNet access to potential targets of Edaravone, the GeneCards, OMIM and TTD databases selected neuroinflammation related genes, get both intersection targets. The protein interaction network was constructed using STRING database and Cytoscape software. GO functional enrichment and KEGG pathway enrichment were analyzed using Metascape database. BV2 microglia were divided into control group, lipopolysaccharide activated group and lipopolysaccharide plus Edaravone group. The expression changes of TDP-43, cGAS, STING, TNF-α and IL-1β were detected by western blot and immunofluorescence staining. Results Network pharmacology identified 70 potential targets of Edaravone in regulating neuroinflammation, with 1339 GO and 157 KEGG pathways enriched. Western blot and immunofluorescence staining showed that, compared with the control group, the expression of TDP-43, cGAS and STING, as well as inflammatory factors TNF-α and IL-1β were increased in activated BV2 microglia, while the expressions of these factors were decreased after Edaravone intervention. Conclusions Edaravone can inhibit TDP-43/cGAS/STING signaling in BV2 cells to reduce inflammation.
关键词
依达拉奉； /
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TAR DNA结合蛋白43； /
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环鸟苷酸-腺苷酸合成酶； /
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干扰素基因刺激因子； /
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神经炎症； /
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网络药理学
Key words
Edaravone; /
TDP-43; /
cGAS; /
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STING; /
Neuroinflammations; /
Network pharmacology
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基金
国家自然科学基金（81960223）；云南省-昆明医科大学联合专项（202301AY070001-163）；云南省教育厅科学研究基金研究生项目（2024Y206）
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