Objective: To study the protective effect and mechanism of augmenter of liver regeneration (ALR) on mice with acute liver injury.
Methods: Thirty BALB/c mice were randomly divided into normal control group, acute liver injury group and ALR intervention group. Acute liver injury group was given intraperitoneal injection of the mixture (2 mL/kg body mass once) of CCl4 (500 mL/L) and mineral oil. ALR intervention group was given ALR plasmid by tail intravenous injection 8 hours before CCl4 injection. The control group was injected the same amount of normal saline. The pathological changes of liver tissue were detected by HE staining. The serum was collected for detecting alanine transaminase (ALT) and aspartate transaminase (AST). The frequency of regulatory T cells (Tregs) in liver tissue was analyzed by flow cytometry. The mRNA levels of Foxp3, ALR, interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) were measured by real-time quantitative PCR (qRT-PCR).
Results: The expression level of ALR mRNA in ALR intervention group was significantly higher than that in acute liver injury group and in normal control group; no statistically significant difference was found between the latter two groups. The frequency of Tregs in liver tissue had significant differences among these groups; CD25⁺Foxp3⁺Treg/CD4⁺T level was higher in ALR intervention group [(5.90 ± 0.10)%] than in acute liver injury group [(4.23 ± 0.46)%] and in normal control group [(2.93 ± 0.74)%]; and it was higher in acute liver injury group than in normal control group. The expression level of Foxp3 mRNA in liver tissue had the same trend as the results of flow cytometry. It was higher in ALR intervention group than in acute liver injury group and in the normal control group. The mRNA levels of IL-6 and TNF-α in ALR intervention group decreased as compared with acute liver injury group; the mRNA levels of IL-6 and TNF-α in acute liver injury group significantly increased as compared with the control group.
Conclusion: ALR can protect mice against acute liver injury by up-regulating the expression of Tregs, which may be related to Tregs-mediated down-regulation of inflammatory cytokines IL-6 and TNF-α.