Effect of endotoxin tolerance on D-GalN/LPS induced fine structure change of liver and cytokine in rats

Objective To study the fine structure changes of liver and the level of cytokine in endotoxin tolerant rats received intraperitoneal injections of GalN/LPS.Methods Endotoxin tolerance(ET)model of SD rats was induced by five daily intraperitoneal injections of 011mg/kg LPS.Normal control rats received intraperitoneal injections of the same volume saline.Then the rats were injected with D-GalN 800 mg/Kg and LPS 8μg/rat.On the sixth day,liver tissue and blood were collected 24 hours after the injection of D-GalN/LPS.Liver histopathology and fine structure of each group were observed by HE staining and electron microscope.The level of TNF-αand IL-6 were estimated by ELISA and the concentrations of endotoxin were determined by tachypleus amebocyte lysate.Results GalN/LPS induced acute liver injury was attenuated significantly by LPS pretreatment.The plasma ALT,AST and TBiL activity were decreased remarkably by LPS pretreatment.The concentrations of endotoxin and the TNF-αand IL-6 level were evidently lower in ET group than those in the ALF group.Conclusion LPS pretreatment could induce endotoxin tolerance of rat,which made decreased releases of TNF α,IL-6 and endotoxin.The alleviation of GalN/LPSinduced acute liver injury in ET rats suggested that ET could be used to reduce severe liver injury.