Abstract:

Objective To establish liver  injury rat models with lipopolysaccharide (LPS) and investigate the protective effect of erythropoietin (EPO) on liver injury and its possible mechanism,and to provid  evidence for the treatment of liver injury induced by LPS. Methods 40 adult Wistar rats were randomly divided into blank control group(n=10),EPO control group(n=10),LPS group(n=10) and LPS + EPO group(n=10). The  liver injury rat models were established by injecting 10 mg/kg LPS into the tail vein of  rats in LPS and LPS+EPO groups,while the rats in  control group received the same amount of saline. 30 min later,the rats in LPS + EPO group and EPO control group were given rhEPO (5 000 U/kg) via the tail vein injection,while the rats in the other  two groups were given saline.5 rats were killed in each group after 6 and 24 h,and the levels of serum enzymes including aspartate aminotransferase (AST) and alanine transarninase (ALT) were evaluated by biochemical analysis and the tumor necrosis factor-α (TNF-α) was determined by immunoradiometric assay. The other rats were killed at 24 h,the liver tissue sections were underwent histological examination by hematoxylin and eosin (HE) staining under light microscope. The ultrastructure changes of liver tissues were assessed by transmission electron microscope (TEM).The expressions of AKT,P-AKT and NF -κB were determined by Western blotting. Results Compared with control group,the levels of ALT,AST,and TNF-α in LPS and LPS + EPO groups were elevated(P<0.05);the levels in LPS group were increased significantly compared with LPS+EPO group (P<0.05). Compared with control group,the expressions of AKT,NF-κB in LPS group were enhanced; compared with  LPS group,the expressions of P-AKT and NF-κB in LPS+EPO group were decreased. The light microscope results showed the inflammatory  cells presented  infiltration and swelling or necrosis of liver cells in the liver tissue in LPS group,and the inflammatory cell infiltration and  hepatocyte swelling were also visible in LPS+EPO group,but much slightly. The electron microscope results  showed that the  hepatocyte mitochondrial presented swelling,disappearance of microvilli,vacuolization of liver cells in LPS group,and the similar injury was visible in LPS+EPOgroup,but much slightly. Conclusion EPO can protect the LPS-induced liver injury by reducing inflammatory and tissue degeneration which may be related with phosphatidylinositol 3-kinase (PI3K)/AKT/NF-κB signal pathway .

Key words: erythropoietin;lipopolysaccharide;liver injury