Abstract: Objective To build and compare two liver fibrosis models using uPA knock-out (uPA-/-) mice and wild-type (WT) mice. Methods Adult male C57BL/6J WT mice and uPA knock-out (uPA-/-) mice were divided into four groups with 10 mice in each group: control groups (WT, uPA-/-) and liver fibrosis model groups (WT, uPA-/-). Mice were injected intraperitoneally with 0.15ml 10% CCl₄ (or olive oil as control) 2 times per week for 4 weeks and 6 weeks respectively. Serum alanine aminotransferase (ALT), aspartate(AST), albumin(ALB) and albumin/globulin(A/G) were determined, liver hydroxyproline (Hyp) level was determined using hydrochloric acid hydrolysis method and serum procollagen III (PC III) content was measured by radioimmunoassay; liver histopathology were performed using HE staining and Masson staining. Results After modeling for 4 weeks and 6 weeks, serum ALT and AST activity of both WT mice and uPA-/- mice significantly increased while serum Alb content significantly decreased comparing with control (P<0.01); at 4 weeks, significant decrease of A/G content was found in uPA-/- mice model only (P<0.01). After modeling for 4 weeks and 6 weeks, serum PCⅢ level and liver Hyp content of uPA-/- mice model significantly increased comparing with control (P<0.01); At 6 weeks, serum PCⅢ level and liver Hyp content of WT mice models started to increase significantly (P<0.01), and the elevated values were not as high as those in uPA-/- mice model. Histopathology showed that the degree of liver fibrosis in uPA-/- mice model was more severe than that in WT mice model. Conclusion Compared with C57BL/6J WT mice, establishment of liver fibrosis model by using uPA-/- mice was required shorter time and showed more severe degree of liver fibrosis.

Key words: uPA knock-out mice, CCl₄, Liver fibrosis, Animal model