The therapeutic effect of koumine on acute liver injury in mice with sepsis and its mechanisms
HUANG Hui-hui
LUO Yu-fei
CHEN Jin-xing
JIN Gui-lin
YU Chang-xi
YANG Jian
Abstract：Objective:To explore the therapeutic effect and possible mechanisms of koumine (KM) on lipopolysaccharide (LPS)-induced sepsis and acute liver injury in mice.Methods:A total of 48 C57BL/6 mice were randomly divided into control group,model group,MCC95010 mg·kg-1 group and KM 7.5,15,30 mg·kg-1 groups,with eight mice in each group.Mice were given a one-time intraperitoneal injection of the corresponding drugs or an equal volume of normal saline.1 h later,the mice in the control group were given equal volume of normal saline,and those in the other groups were given 1 mg·kg-1 LPS intraperitoneally to construct an LPS-induced sepsis mouse model.4 h after LPS administration,serum aspartate aminotransferase ( AST ) and alanine transaminase ( ALT ) activities were detected by automatic biochemical analyzer.The serum AST and ALT activities were determined by an automatic biochemical analyzer.The levels of interleukin-1β in serum and peritoneal lavage fluid were measured by an ELISA kit.RT-qPCR was used to detect the mRNA levels of nucleotide binding oligomerization domain like receptor protein 3 (NLRP3),cysteine aspartic protease-1 precursor (pro-caspase-1),apoptosis-associated speck-like protein containing a CARD ( ASC),IL-1β precursor ( pro-IL-1β),tumor necrosis factor-α ( TNF-α) and IL-6 in liver tissue.Results:KM significantly decreased the serum levels of AST and ALT in sepsis mice and markedly decreased the levels of IL-1β in serum and peritoneal lavage fluid.The pathological section of liver showed that the degree of tissue damage after KM treatment was slightly reduced than that in the model group.RT-qPCR results confirmed that KM significantly decreased the mRNA expression levels of inflammatory factors TNF-α and IL-6,and significantly decreased the mRNA expression levels of NLRP3 inflammator-related proteins including NLRP3,pro-caspase-1,ASC and pro-IL-1β in liver tissue of model mice.Conclusion:KM shows a significant therapeutic effect on acute liver injury in mice with sepsis,and its mechanisms may be attributed to inhibiting the activation of NLRP3 inflammasome and the release of related pro-inflammatory cytokines.
Keywords：kouminesepsisliver injurynucleotide binding oligomerization domain like receptor protein 3interleukin-1β
Publication Date：2024-12-31
Online Publishing Date：2026-08-14(First online date of this platform, not the publication date of the document)
Pages：7( 2555-2561 )