ObjectiveTo explore the protective effect and underlying mechanism of epigallocatechin gallate (EGCG) in sepsis-induced acute liver injury.MethodsMale C57BL/6J mice aged 8-10 weeks old were randomly divided into cecal ligation and puncture (CLP) group (sepsis-induced acute liver injury model mice), CLP+EGCG low-dose (4 mg/kg, injected subcutaneously) group, CLP+EGCG high-dose (8 mg/kg, injected subcutaneously) group, and sham group (n＝6). According to the intervention methods, human liver cells (L02 cells) were divided into lipopolysaccharide (LPS) (400 ng/mL, cell model of sepsis-induced acute liver injury) group, LPS (400 ng/mL)+high mobility group protein B1 (HMGB1) (100 ng/mL) group, LPS (400 ng/mL)+EGCG (100 μg/mL) group, and control (PBS treatment) group. The whole blood of mice was collected and the liver tissues were isolated 24 h after operation. The routine blood test and liver function of mice were detected by automatic biochemical analyzer, and the pathological changes of liver tissues were observed by hematoxylin-eosin (H-E) staining. The expression of inflammatory factors (HMGB1, tumor necrosis factor α[TNF-α], and interleukin[IL]-6) in mouse serum and L02 cell supernatant was detected by enzyme-linked immunosorbent assay. The expression of HMGB1, Toll-like receptor 4 (TLR4), nuclear factor κB (NF-κB) p65, nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3) and pyroptosis-related proteins (gasdermin D [GSDMD], cysteine aspartic acid specific protease [caspase] 1, caspase 11, IL-1β, and IL-18) was detected by Western blotting. The expression and localization of HMGB1 and GSDMD in mouse liver tissues were analyzed by immunohistochemical staining.ResultsThe white blood cell count, lymphocyte count, neutrophil count and monocyte count in the CLP group were significantly lower than those in the sham group (all P < 0.05), and the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were significantly higher than those in the sham group (both P < 0.01), indicating that the sepsis-induced acute liver injury mouse model was successfully constructed. Compared with the CLP group, the expression levels of ALT, AST, HMGB1, TNF-α and IL-6 in the CLP+EGCG low-dose and high-dose groups were significantly decreased (all P < 0.05), and these indexes were significantly lower in the CLP+EGCG high-dose group than in the CLP+EGCG low-dose group (all P < 0.05). The results of H-E staining showed that the liver tissue injury in the CLP+EGCG low-dose and high-dose groups was less than that in the CLP group, especially in the high-dose group. The expression levels of HMGB1, TLR4, NF-κB p65, NLRP3 and pyroptosis-related proteins in the liver tissues of the CLP+EGCG low-dose and high-dose groups were significantly lower than those in the CLP group (all P < 0.05), and the decrease was more significant in the high-dose group (all P < 0.05). Immunohistochemical staining showed that GSDMD was localized in the cytoplasm of liver cells, while HMGB1 was localized in both cytoplasm and nucleus; the expression levels of HMGB1 and GSDMD in the CLP+EGCG low-dose and high-dose groups were significantly lower than those in the CLP group (all P < 0.05), and the decrease was more significant in the high-dose group (both P < 0.05). Compared with the LPS+HMGB1 group, the expression levels of HMGB1, TNF-α and IL-6 in the cell supernatants of the LPS group, LPS+EGCG group and control group were significantly decreased (all P < 0.05), and the decrease of these 3 indexes in the LPS+EGCG group was more significant than that in the LPS group (all P < 0.05). The expression levels of HMGB1, TLR4, NF-κB p65, NLRP3 and pyroptosis-related proteins in the LPS+HMGB1 group were significantly higher than those in the LPS, LPS+EGCG and control groups (all P < 0.05), and the expression levels of the above-mentioned proteins in the LPS+EGCG group were significantly lower than those in the LPS group (all P < 0.05).ConclusionEGCG has some protective effect on sepsis-induced acute liver injury, and the underlying mechanism may be related to alleviating hepatocellular pyroptosis by attenuating the HMGB1/TLR4/NF-κB/NLRP3 pathway.