METHANE-RICH SALINE PROTECTS AGAINST SEPSIS-INDUCED LIVER DAMAGE BY REGULATING THE PPAR-gamma/NF-kappa B SIGNALING PATHWAY

摘要

Sepsis, a life-threatening organ dysfunction due to a dysregulated response to infection, is a common complication of major surgery. Previous studies have shown that methane possesses protective properties. This study aims to investigate the protective effect of methane-rich saline (MRS) on sepsis-induced liver injury. In an in vivo experiment, C57BL/6 mice received cecal ligation and puncture to create a septic model followed by MRS treatment (10 mL/kg, ip treatment) 30 min and 12 h after the operation. We found that methane effectively decreased the serum aspartate aminotransferase, alanine aminotransferase and liver index, as well as the liver pathological damage, and reduced the localized infiltration of inflammatory cells. Methane suppressed the expression of the toll-like receptor 4/nuclear factor-kappa B (NF-kappa B) signaling pathway and stimulated the expression of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) during sepsis, which inhibited the activation of NF-kappa B and decreased the level of inflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-6, and interleukin-1 beta. Moreover, we found that MRS treatment relieved reactive oxygen species (ROS) damage by upregulating heme oxygenase-1, superoxide dismutase and glutathione, and downregulating malondialdehyde, which was consistent with the results of dihydroethidium fluorescent staining. MRS treatment also regulated apoptosis-related proteins, such as Bax, Bcl-2, and caspase-3. In the in vitro experiment, HepG2 cells received inflammatory stimulation induced by LPS followed by methane-rich medium (MRM) treatment. We found that MRM alleviated the inflammatory damage, ROS damage and regulated the expression of PPAR-gamma/NF-kappa B. Our data indicated that methane treatment prevented liver damage in sepsis via anti-inflammatory, anti-oxidative, and anti-apoptotic properties that involved the PPAR-gamma/NF-kappa B signaling pathway.