Nan Fang Yi Ke Da Xue Xue Bao. 2025 Jul 20;45(7):1527-1534. doi: 10.12122/j.issn.1673-4254.2025.07.20.
ABSTRACT
OBJECTIVES: To prepare a stable mouse model of chronic liver fibrosis induced by dietary vitamin A (VA) deficiency combined with CCl4 injections.
METHODS: A total of 126 Balb/c mice were randomized into 3 groups for feeding with a normal VA diet or a VA-deficient diet containing 500 or 200 IU/kg VA. After 4 weeks of feeding, half of the mice in each group were given intraperitoneal injections of 5% CCl4 (10 mL/kg, twice a week) for 8 weeks. Serum retinol, ALT/AST and liver index of the mice were examined, liver tissue pathologies were observed with HE and Masson staining, and liver fibrosis score and oxidative stress level were evaluated.
RESULTS: Four weeks of VA-deficient feeding, especially at 200 IU/kg, significantly lowered serum retinol level of the mice. CCl4 injections for 8 weeks obviously increased liver index and ALT/AST and caused obvious liver fibrosis in all the mice, but liver pathologies were more severe in the 2 VA-deficient groups; severe liver necrosis with inflammatory cell infiltration was observed in 200 IU/kg VA group, where 2 mice died. After discontinuation of CCl4, the mice with normal dietary VA showed gradual recovery of the liver index, ALT/AST, liver cord structure and liver fibrosis; the mice with VA deficiency, however, showed no significant improvements in these parameters, and the mice with 200 IU/kg VA still had serious abdominal adhesion, false lobules and massive inflammatory cell infiltration with a fibrosis stage score of 3. The oxidative damage index 8-OHdG was significantly higher in 500 IU/kg VA group than in normal VA group after CCl4 modeling.
CONCLUSIONS: Feeding with diet containing 500 IU/kg VA for 4 weeks and 10 mL/kg CCl4 injections for 8 weeks can result in stable moderate to severe liver fibrosis in mice without spontaneous reversal at 8 weeks of drug withdrawal.
PMID:40673316 | DOI:10.12122/j.issn.1673-4254.2025.07.20
