Liraglutide Ameliorates Brain Injury in Septic Mice by Inhibiting NLRP3 Inflammasome Signaling Pathway
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.
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维普
