冷诱导RNA结合蛋白在脓毒症肝损伤中的作用及其机制OA

Objective To investigate the role of cold-inducible RNA-binding protein(CIRP)in sepsis-induced liver injury and its potential as a therapeutic target.Methods Serum CIRP level was measured in 30 sepsis-induced liver injury patients and 15 healthy volunteers by ELISA,and its correlation with clinical scores was analyzed.Wild-type(WT)and CIRP-knockout(Cirp⁻/⁻)mouse models of sepsis were established using cecal ligation and puncture(CLP),and liver pathological injury,inflammatory responses,and neutro-phil extracellular trap(NET)formation were evaluated.The therapeutic effect of targeting CIRP was validated by intravenous injection of a CIRP-targeting aptamer in septic mice.Results Serum CIRP level was significantly higher in sepsis-induced liver injury patients than in healthy volunteers[(992.5±456.7)pg/mL vs(328.5±145.7)pg/mL,P<0.001].Serum CIRP concentrations were positively correlated with APACHE Ⅱ score and ALT level(P<0.01).Compared to WT-CLP group,the mice in Cirp⁻/⁻ CLP group exhi-bited markedly reduced liver necrosis area,inflammatory cell infiltration,and apoptosis,decreased serum ALT,TNF-α,IL-6,and IL-1β levels,and reduced expressions of NET-associated proteins(H3Cit,MPO)(all P<0.05).Treatment with CIRP aptamer alleviated liver injury and lowered ALT and TNF-α levels(all P<0.05).Conclusion CIRP exacerbates sepsis-induced liver injury by promoting NET formation and inflammatory responses.Targeted inhibition of CIRP can significantly reduce NET generation and mitigate liver injury,which highlights its potential as a novel therapeutic target for sepsis-induced liver injury.