西南医科大学学报2025,Vol.48Issue(1):41-46,6.DOI:10.3969/j.issn.2096-3351.2025.01.009
利拉鲁肽通过抑制NLRP3炎症小体信号通路改善脓毒症小鼠脑损伤
Liraglutide Ameliorates Brain Injury in Septic Mice by Inhibiting NLRP3 Inflammasome Signaling Pathway
摘要
Abstract
Objective To investigate the protective effect and underlying mechanism of liraglutide on brain injury in lipopoly-saccharide(LPS)-induced septic mice.Methods Ninety C57BL/6 mice were randomly divided into three groups(n=30):the Con-trol group,the Sepsis group(LPS),and the LPS+Liraglutide group(LPS+Lira).The LPS and LPS+Lira groups received intraperi-toneal injections of LPS(15 mg/kg),while the Control group received an equal volume of normal saline.The LPS+Lira group was sub-cutaneously injected with liraglutide(200 μg/kg)twice daily for 3 consecutive days,starting 2 days before the LPS injection.Results Significant differences were observed among the three groups in terms of survival rate,brain water content,the number of normal pyra-midal cells in the hippocampal CA1 region,apoptosis rate,oxidative stress markers,inflammatory cytokine levels,and related protein expression(P<0.05).Further pairwise comparisons showed that,compared to the Control group,the LPS group had a significantly reduced survival rate(P<0.05),increased brain water content(P<0.05),decreased number of normal pyramidal cells in the hippo-campal CA1 region(P<0.05),and an elevated apoptosis rate(P<0.05).Additionally,oxidative stress and inflammatory cytokine levels were significantly higher(P<0.05),with increased expression of NLRP3,Casp1 p10,Caspase-3,and Bax proteins(P<0.05),and decreased expression of Bel-2(P<0.05).The LPS+Lira group showed significant improvement in all these indicators compared to the LPS group(P<0.05).Conclusion Liraglutide exerts a protective effect against LPS-induced septic brain injury by inhibiting the activation of the NLRP3/Caspase-1 signaling pathway,thereby reducing inflammation,oxidative stress,and apoptosis.关键词
脓毒症/脑损伤/利拉鲁肽/NLRP3炎性体Key words
Sepsis/Brain injury/Liraglutide/NLRP3 Inflammasome分类
基础医学引用本文复制引用
郭焰,杨程杰,母国,魏娜,陈烨,谢冰清,周军..利拉鲁肽通过抑制NLRP3炎症小体信号通路改善脓毒症小鼠脑损伤[J].西南医科大学学报,2025,48(1):41-46,6.基金项目
国家自然科学基金(81873930) (81873930)
四川省科技计划项目(2022YFS0615) (2022YFS0615)
泸州市科技计划项目(2023SYF099) (2023SYF099)