山西医科大学学报2026，Vol.57Issue(7)：778-785,8.DOI:10.13753/j.issn.1007-6611.2026.07.006
二甲双胍经SIRT1/HMGB1通路改善LPS诱导的小鼠小胶质细胞炎症反应
Metformin attenuates LPS-induced inflammatory response in mouse microglia via the SIRT1/HMGB1 pathway
摘要
Abstract
Objective To investigate the effect of metformin(MET)on the inflammatory response induced by lipopolysaccharide(LPS)in mouse microglia(BV2 cells)and explore its underlying mechanism.Methods BV2 cells were cultured in vitro and divided into six groups:CON group,LPS group,L-MET group,M-MET group,H-MET group and H-MET+EX527(a specific SIRT1 inhibitor)group.Cells in CON group were not treated.Cells in LPS group were exposed to LPS at a final concentration of 1 μg/mL for 24 h.Cells in MET groups were incubated with metformin at 0.25,1 and 4 μmol/L for 12 h,respectively,and then stimulated with LPS for 24 h.Cells in H-MET+EX527 group were pretreated with 50 μmol/L EX527 for 1 h,then incubated with 4 μmol/L MET for 12 h,and then stimulated with LPS for 24 h.CCK-8 method was used to assess cell viability,Griess method was used to measure nitric oxide(NO)release,and RT-qPCR and Western blot were employed to detect the mRNA and protein expression levels of SIRT1,HMGB1,TLR4 and NF-κB.Simultaneously,a co-culture system of BV2 cell-conditioned medium and mouse neuronal cells(HT22 cells)was used as an experimental model,and the viability of HT22 cells was measured to evaluate the indirect neuroprotective effect of MET.Results Compared with CON group,NO release increased in LPS group(P<0.01),SIRT1 expression was down-regulated(P<0.05),and expressions of HMGB1,TLR4,and NF-κB were up-regulated(P<0.05),and viability of HT22 cells decreased under co-culture condi-tions(P<0.05).Compared with the LPS group,SIRT1 expression was significantly increased in all MET groups(P<0.05),whereas the expressions of HMGB1,TLR4 and NF-κB,as well as NO release,were significantly decreased(P<0.05),with the effects becoming more pronounced at higher MET concentrations.Meanwhile,the viability of HT22 neurons was significantly enhanced(P<0.05).Compared with the H-MET group,the H-MET+EX527 group showed decreased SIRT1 expression(P<0.05),elevated expressions of HMGB1,TLR4 and NF-κB,and increased NO release(P<0.05),along with a decline in HT22 cell viability back to lower levels(P<0.05).Conclusion Metformin may inhibit LPS-induced BV2 microglial activation and significantly alleviate neuroinflammatory responses through regulation of the SIRT1/HMGB1 signaling pathway.关键词
二甲双胍/神经炎症/小胶质细胞/脂多糖/SIRT1/HMGB1信号通路Key words
metformin/neuroinflammation/microglia/lipopolysaccharide/SIRT1/HMGB1 signaling pathway分类
医药卫生引用本文复制引用
张珂浛,李刘艳,袁可馨,史双僖,惠晨曦,吴锋,司开卫,张丹..二甲双胍经SIRT1/HMGB1通路改善LPS诱导的小鼠小胶质细胞炎症反应[J].山西医科大学学报,2026,57(7):778-785,8.基金项目
陕西省重点研发计划项目(2025SF-YBXM-323,2023-YBSF-178) （2025SF-YBXM-323,2023-YBSF-178）
国家级大学生创新训练计划项目(S202310698207) （S202310698207）
