中国医科大学学报2026，Vol.55Issue(8)：713-719,727,8.DOI:10.12007/j.issn.0258-4646.2026.08.007
右美托咪定通过上调Nur77抑制脂多糖诱导的巨噬细胞糖酵解和炎症反应
Dexmedetomidine inhibits LPS-induced inflammatory response and glycolysis in macrophages by upregulating Nur77
摘要
Abstract
Objective To investigate whether dexmedetomidine(Dex)regulates glycolysis and inflammatory responses in septic mac-rophages through Nur77.Methods The Gene Expression Omnibus database was used to analyze the correlation of Nur77 with glycoly-sis-related and inflamation-related genes.The murine leukimia monocyte/macrophage RAW264.7 cells were divided into control,lipopoly-saccharide(LPS),dexmedetomidine treatment(Dex+LPS),Nur77 inhibitor(DIM)+LPS,Dex+DIM+LPS groups.Western blotting was performed to detect Nur77 protein expression.Real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay were used to measure the mRNA and protein levels of the inflammatory cytokines IL-1β,IL-10,and TNF-α.Lactate content and the NAD+/NADH ratio were measured to assess glycolysis levels.Results Bioinformatics analysis revealed that glycolytic gene expression peaked 2 hours after LPS stimulation,while the inflammatory response peaked at 6 hours,with a significant positive correlation between the glyco-lysis pathway score and inflammation score(r=0.77,P=0.034),suggesting that glycolysis activation precedes and promotes inflamma-tory response.In cell experiments,compared with the LPS group,the Dex+LPS group exhibited significantly higher Nur77 expression,lower levels of pro-inflammatory cytokines IL-1β and TNF-α,higher levels of the anti-inflammatory cytokine IL-10,reduced lactate con-tent,and an elevated NAD+/NADH ratio.The Nur77 inhibitor,DIM,partially reversed the effects of Dex.Furthermore,Nur77 expression had a significant negative correlation with the glycolytic enzymes GAPDH and PDK1,while Nur77 knockout increased the expression of glycolysis-and inflammation-related genes.Conclusion Glycolysis activation is associated with the inflammatory response during sepsis,and Dex inhibits LPS-induced macrophage glycolysis and inflammatory responses by upregulating Nur77 expression,thereby exerting protective effects in sepsis.关键词
右美托咪定/脓毒症/巨噬细胞/Nur77/糖酵解/炎症反应Key words
dexmedetomidine/sepsis/macrophage/Nur77/glycolysis/inflammatory response分类
医药卫生引用本文复制引用
王家锴,刘贤,毕红英,付建宇,刘旭..右美托咪定通过上调Nur77抑制脂多糖诱导的巨噬细胞糖酵解和炎症反应[J].中国医科大学学报,2026,55(8):713-719,727,8.基金项目
国家自然科学基金(81701958) （81701958）
贵州省卫生健康委科学技术基金(gzwkj2025-206) （gzwkj2025-206）
