The Protective Effects And Mechanism Of Vitamin D₃ On Experimental Hepatic Injury In Mice

Objective: To investigate the effects and mechanism of vitamin D3 on liver function, liver fibrosis, liver pathology,and ultramicrostructure, acute liver injury was produced in BALB/C mice by CCl4. Methods: Twenty five BALB/C mice were randomly and equally divided into five groups: control group, vehicle group, and three vitamin D3 groups(n = 5 for each group). Doses of vitamin D3 were 15μg,7.5μg, lμg in the vitamin D3 groups(daily, intraperitoneal), which were indicated as high, medium and low does.Mice in control group and vehicle group were daily intraperitoneal injected with 0.9%Nacl. After the two weeks treatment, vehicle group and treatment groups were intraperitoneal injected with 0.1%CCl4 in olive(0.2ml/2d, ip) 7 days later. Meanwhile, the control group was equivalently intraperitoneal injected with 0.9%Nacl daily. At the end of administration of CCl4 solution, blood and liver tissue were harvested from all the mice. Alanine aminotransferase(ALT) and Aspartate transaminase(AST) were detected with routine biochemical method. Hyauline(HA), collagen type IV(IVC), laminin(LN), and collagen typeⅢN-terminal peptide(PⅢNP) were detected with RIA. Pathological changes in liver tissues were analyzed by HE staining, reticular fiber staining and Masson staining.The ultramicrostructural change of hepatic tissue was observed with electron microscope. The expression of splenic vitamin D receptor(VDR) m RNA and serum 25(OH)D3 was detected by using RT-PCR and HPLC-MS/MS, respectively.Results: The levels of liver index, ALT, AST, HA, LN, PⅢNP, CⅣ were significantly higher in the vehicle group than that in the control group(all P<0.01). Compared with vehicle group, the levels of serum liver index, ALT, AST,HA,LN, PⅢNP, CⅣ were significantly debased after the treatment with vitamin D3(all P<0.01).The levels ofserum 25(OH) D3 in control group were higher than that in vehicle group, but this difference was not statistically significant(P>0.01).The serum 25(OH)D3 and VDR gene expression in vitamin D high and middle group were higher than those in the normal and model groups(P<0.05). The VDR gene expression in vitamin D high group was significantly higher than that in low group(P<0.05). The improvement of liver pathology and ultramicrostructure in the treatment groups was superior to that in the vehicle group obviously.Conclusion: Vit D3 has the protective effects of liver function in the experimental liver injury of mice. Vit D3 has anti-inflammation and anti-fibrosis effects in the mice experimental liver injuries induced by CCl4, by reducing level of serum fibrosis in early liver fibrosis. Vit D3 has significant protective effects on the hepatic ultramicrostructure damage in experimental hepatic injury mice model,and its mechanism of action was associated with up-regulation of VDR gene expression.