Establishment of a new acute-on-chronic liver failure model

摘要

To establish an animal model of acute-on-chronic liver failure (ACLF) that would replicate the pathological process of ACLF in humans, rats were administered porcine serum (PS) for 11 weeks. Liver fibrosis was determined by pathological and biochemical assessments. The animals then were injected with d-galactosamine (d-gal) and lipopolysaccharide (LPS). The survival times of animals with cirrhosis and ACLF were determined over 48h. Other animals were killed at 0, 4, 8 and 12h after administration of d-gal/LPS. Liver injury was assessed by histopathological analysis and biochemical indices, and apoptosis was detected by Western blot and TUNEL analysis. After PS administration for 11 weeks the serum levels of hyaluronic acid and N-procollagen type III peptide increased significantly, and serious fibrosis and cirrhosis was observed at weeks 10 and 11. Cirrhotic rats were injected with d-gal/LPS to induced ACLF; the rate of mortality over 48h was 80%. ALT and AST levels increased markedly at 4h, but decreased significantly at 8 and 12h post-treatment. The total bilirubin, direct bilirubin, and total bile acids levels increased markedly at 8 and 12h. Clotting times, TNF-@a and IL-6 levels increased significantly, except for 12h post-treatment. Apoptosis, inflammation and necrosis were elevated as determined by hematoxylin-eosin staining and TUNEL assays. BCL-2 levels decreased significantly, While BAX levels increased significantly. Cytochrome c expression peaked at 8h post-d-gal/LPS treatment. In conclusion, an ACLF model induced by PS and d-gal/LPS was established and the underlying mechanisms of ACLF development were explored.