Characterization of a reproducible mouse model of hepatic veno-occlusive disease

Abstract

Objective To establish a reproducible mouse model of hepatic veno-occlusive disease (HVOD) after allogeneic bone marrow transplantation (aallo-ABMT) and explore its pathogenesis.Methods Balb/c mice were randomly divided into three groups:(1) normal saline (NS) control group; (2) total body irradiation (TBI) group; (3) allogeneic bone marrow transplantation (allo-BMT) group.Liver weight,total bilirubin (TBil),tumor necrosis factor α (TNF-a),interleukin 6 (IL-6) and monocyte chemotactic protein 1 (MCP-1) were detected on the day 0,5,10,15 and 20 after transplantation.Hepatic vein and sinusoid congestion,infiltration of inflanmatory cells,and damage to hepatic cells and vascular endothelial cells were observed under the light microscopy after HE staining.Fibrosis of hepatic sinusoids and venule was observed under the light microscopy after Masson staining.Results Liver weight and TBil levels were elevated at 5th day and reached the peak at 15th day after all-ABMT.The changes of hepatic congestion and edema were obviously observed and there was infiltration of inflammatory cells at 5th and 10th day after alloABMT.At 15th and 20th day,hepatic congestion,edema and necrosis were reduced and liver damage was mainly presented with liver fibrosis and inflammatory infiltration.All mice died within 10 days after TBI,and hepatic congestion and edema were aggravated.As compared with NS control group,TNF-α,IL-6 and MCP-1 concentrations were significantly increased after all-ABMT.Conclusion A reproducible mouse model of hepatic veno-occlusive disease after all-ABMT was successfully established,and the pathogenesis was closely related to endothelial damage caused by total body irradiation,inflammatory cell infiltration and increased concentrations of cytokines. Key words: Hematopoietic stem cell transplantation; Endothelial cells; Hepatic veno-occlusive disease; Cytokines