[摘要]：Background. Liver transplantation is the only therapy of proven benefit in fulminant hepatic failure (FHF). Lipopolysaccharide (LPS), D-galactosamine (GalN)-induced FHF is a well-established model of liver injury in mice. Erythropoietin has a powerful tissue-protective effect in animal models. The aim of this study was to investigate the effect and mechanism of recombinant human erythropoietin (rhEPO) administration in FHF mice. Methods. C57BL/6 (n = 42) mice were studied in vivo in a fulminant model induced by GalN/LPS. rhEPO was administered 30 min after the induction of FHF. Serum liver enzymes and hepatic tumor necrosis factor (TNF)-alpha and interleukin (IL)-1 beta levels were determined. Histologic analysis was performed, and apoptotic cells were identified by immunohistochemistry for caspase-3. Nuclear factor (NF)-kappa B and c-Jun-N-terminal kinase (JNK) activation were studied using Western blot analysis. Results. After the induction of FHF, all control mice died within 12 hr of GalN/LPS administration. However, 83% of mice that were administered rhEPO were alive 2 weeks later, and overall survival improved (Kaplan-Meier, P < 0.001). The serum liver enzymes, hepatic TNF-alpha and IL-1 beta levels, liver histologic injury, and apoptotic hepatocytes were significantly reduced in FHF mice that were administered rhEPO compared with untreated mice. A significant decrease in hepatic NF-kappa B and JNK activation was noted in FHF rhEPO-treated mice compared with FHF untreated mice. Conclusions. The administration of rhEPO brought about increased survival and attenuation of the hepatic injury. This was associated with decreased hepatic NF-kappa B and JNK activation and thus TNF-alpha and IL-1 beta levels. These findings have important implications for the potential use of rhEPO in FHF.
