Level of TLR4 in the liver of rats with multiple organ dysfunction syndrome

Abstract

Objective To determine the level of toll-like receptor 4 (TLR4) in the liver of rats with the multiple organ dysfunction syndrome (MODS), and to investigate the early phase of liver damage in MODS. Method Forty adult male Spraque-Dawley (SD) rats were randomly (random number) divided into two groups, namely the normal control group and the MODS model group. The rats of model group were further divided into 4 sub-groups as per different intervals, 6 h, 12 h,24 h and 48 h, and there were 8 rats in each subgroup. The animal models of MODS were established by two hits in which at first the left eyeball of rat model was removed to bleed to 2 mL/100 g, and four hours later, lipopolysaccharide (LPS, 5 mg/kg) was injected into intraperitoneal cavity of model rats. The same volume of saline instead of LPS was injected intraperitoneally into rats of control group. All rats were sacrificed at different intervals. The histological changes in the liver tissue were observed by naked eye and under light microscope. The levels of TRL4 protein in serum and liver tissue were detected by using flow cy-tometry (FCM). One-way ANOVA was used for comparison among multiple groups. Results (1) There were no histopathological changes in liver of rats in control group, and the liver damage was serious in rats with MODS. (2) Compared withrats of control group, the expression of TLR4 in liver tissue of rats with MODS increased in 6 hours and reached peak 12 hours later (P < 0.01), and then decreased 24 hours after. There was significant difference in level of TLR4 between two groups 48 hours after. Compared with rats of control group, the level of TLR4 in peripheral blood leucocytes of rats with MODS increased significantly 6-48 hours after LPS (P < 0.01).Conclusions The level of TLR4 markedly increases in the liver tissue at early stage of MODS. The TLR4 may play an important role in the pathogenesis of liver injury in MODS, and the TLR4 may become a novel therapeutic target in MODS. Key words: Multiple organ dysfunction syndrome (MODS); Toll-like receptor4 (TLR4); lipopolysacchar-ide(LPS); Systemic inflammatory response syndrome(SIRS); Liver tissue; Two hits; Rat