Trichostatin A improves the inflammatory response and liver injury in septic mice through the Fox03a/ autophagy signaling pathway

Abstract

BACKGROUND: Sepsis-induœd liver injury is a fatal complication of sepsis. Trichostatin A (TSA) regulates inflammation and autophagy In some human diseases, and forkhead box 03a (Fox03a) has been shown to regulate autophagy The present study alms to Investigate whether TSA exerts its effects on septic liver injury through the FoxOSa/autophagy signaling pathway METHODS: A sepsis mouse model was constructed by the cecal ligation and puncture (CLP) method, and AML12 cells were pretreated with llpopolysaccharide (LPS) (1 |jg/mL) to establish a sepsis cell model. Forty mice were divided into four groups, namely control group, TSA group, CLP group, and CLP+TSA group, with 10 mice In each group. Cells were divided into control group, TSA group, LPS group, and LPS+TSA group. Hematoxylln-eosin (H&E) staining and biochemical methods were used to evaluate liver tissue Injury. Enzyme-linked Immunosorbent assay (ELISA) was applied to detect the expression of proinflammatory cytokines, and Western blotting and Immunofluorescence were used to measure autophagy-related protein expression. RESULTS: Compared with the CLP group (mice), the proinflammatory cytokines (Interleukln-P [IL-p] 2,665.27±324.90 pg/mL to 2,080.26±373.66 pg/mL; lnterleukln-6 [IL-6] 399.01 ±60.98 pg/mL to 221.90±46.89 pg/mL) and the hepatocyte Injury markers (aspartate transaminase [AST] from 198.18±27.07 U/L to 128.42±20.55 U/L; alanine aminotransferase [ALT] from 634.98±74.10 U/L to 478.60±32.56 U/L) were notably decreased after TSA Intervention. Moreover, LC3 II and Fox03a showed an obvious increase and P62 showed an obvious decrease in the CLP+TSA group. Cell experiment results showed the similar trend. After Fox03a gene was knocked down In AML12 cells, the promotion of autophagy and the Improvement of liver enzyme index and inflammation by TSA were weakened. CONCLUSION: TSA may improve the Inflammatory response and liver injury In septic mice through Fox03a/autophagy