Maresin-1 Alleviates Sepsis-Induced Liver Injury by Regulating Apoptosis and Autophagy via Activation of the PI3K/Akt Signaling Pathway in Mice.

Sepsis-induced liver injury (SILI) stands as an independent prognostic factor for mortality among patients diagnosed with sepsis. Maresin-1 (MaR1) is a proresolving lipid mediator. However, its significance in SILI is uncertain. The current study sought to investigate MaR1's effectiveness in treating SILI, as well as its molecular mechanism. In male C57BL/6J mice, we generated a SILI model by using cecal ligation and puncture (CLP). We further investigated how MaR1 influences inflammation, hepatic autophagy and apoptosis. We showed that treatment with MaR1 ameliorates SILI-induced hepatic injury, as reflected in decreased blood level of the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) enzymes, as well as better appearance of liver tissues. Furthermore, this medication markedly reduced the expression of inflammatory mediators. Importantly, MaR1 inhibited hepatocyte apoptosis by regulating the Bax/Bcl-2 ratio, decreasing cleaved caspase-3 expression, lowering apoptotic cell count, and increasing autophagy. The findings demonstrated that MaR1 treatment reduced p62 protein expression while raising Beclin1 levels and the LC3-II/LC3-I ratio, and facilitated autophagosome formation. The observed effects were most likely due to the stimulation of PI3K/Akt signaling, which was completely prevented by LY294002 (LY), a specific PI3K inhibitor. MaR1's protective effect in SILI may be mediated via stimulation of the PI3K/Akt pathway, which reduces inflammation and regulates apoptosis and autophagy. Our results give additional experimental evidence of the potential therapeutic uses of MaR1 in the treatment of SILI.