The Protection Mechanisms Of S-adenosylmethionine Against Liver Injury Induced By Lipopolysaccharides

Objective Establishing an animal model of endotoxin induced liver damage, observing the expression of liver X receptors (LXR)α, toll like receptor 4 (TLR4) and the important pro-inflammatory cytokines tumor necrosis factor-α(TNF-α) and anti-inflammation cytokines interleukin-10 (IL-10). To explore the effect of SAM reduce LPS liver injury and its possible mechanisms.Methods The mices were randomly divided into three groups. The NS group in which the animals were injected with normal saline. The LPS group in which the animals were intraperitoneally injected with 10 mg/kg LPS. The SAM group in which the animals were pretreated with 100 mg/kg SAM by intraperitoneal injection before 2 hours receiving 10 mg/kg LPS. The survival rate of mices were recorded in 120 hours. The livers of mice were examined for histopathological changes. The levels of TNF-αand IL-10 in the serum were measured using ELISA analysis. The expression of TLR4 and LXRαin hepatic tissues were detected using immunohistochemistry and western blot. According to the type of date, conducting the statistical analysis.Results The SAM can improve the survival rate of mice. The SAM group 50.0%, the LPS group 30.0%, the difference was statistically Significant (P<0.05). The pathological liver damage was showed by microscopy and electron microscopy, the SAM effectively reduced the endotoxin induced liver damage. The SAM group showed significantly lower serum levels of TNF-α(718.83±53.27) pg/ml compared with the LPS group (1791.79±122.19) pg/ml (P<0.05). The SAM group serum levels of IL-10 (418.69±38.77) pg/ml, the peak increase in forward, showed significantly higher than the LPS group (347.09±31.37) pg/ml (P<0.05). The immunohistochemical method (SABC) observing and the western blot testing, the SAM group LXRα(1.605±0.027) was significantly increase in liver, while TLR4 (1.365±0.017) expression was significantly decreased. The LPS group LXRα(1.375±0.014) and TLR4 (1.550±0.034) was statistical different to the SAM group (P<0.05).Conclusions The SAM can significantly reduce the LPS-induced liver injury, the mechanisms may be reduced expression of TLR4 in a variety of cells of liver, and enhance the expression of LXRα, which eventually led to a lower level of TNF-αand a increased level of IL-10.