Abstract: Objective: To observe whether magnesium-L-threonate (MLT) can enhance the antiviral effect of entecavir (ETV) in the HBV-infected mice, and to explore its mechanism. Methods: The recombinant adeno-associated virus 8 carrying 1.3 copies of HBV genome was injected into the C57BL/6 mice by tail vein to establish the HBV persistent infection mouse models. After successful modeling, the mice were divided into model group, MLT group (1.2 g·kg^-1 magnesium-L-threonate capsules), ETV group (75 μg·kg^-1 entecavir tablets), and combined treatment group (1.2 g·kg^-1 magnesium-L-threonate caspules+75 μg·kg^-1 entecavir tablets) (n=8), and another 8 normal mice uninfected with HBV were selected as control group. Then all the mice were intragastrically administered for 4 weeks. The serum levels of HBsAg and HBeAg were detected by ELISA method, the copied of HBV DNA in liver tissue and serum of the mice were detected by quantitative real-time PCR. The peripheral blood CD8+ T cells were isolated, and the contents of Mg²⁺ in serum and CD8+ T cells were detected. The expression levels of PD-1, NKG2D, CD95 and CD38 in the CD8+ T cells were detected by flow cytometry. Results: Compared with control group, the contents of Mg²⁺ in serum and CD8+ T cells and the expression levels of surface activation molecules NKG2D and CD38 in the CD8+ T cells in model group were significantly decreased (P<0.05), while the expression levels of surface inhibitory molecules PD-1 and CD95 in the CD8+ T cells were significantly increased (P<0.05). Compared with model group, the expression levels of serum HBsAg and HBeAg, and the copied of HBV DNA in liver tissue and serum of the mice in various administration groups were significantly decreased (P<0.05), and the improvement degree of the indexes in combined treatment group was superior to other administration groups. Compared with model group, the contents of Mg²⁺ and the expression levels of NKG2D and CD38 in MLT group and combined treatment group were significantly increased (P<0.05), the expression levels of PD-1 and CD95 were significantly decreased (P<0.05), but there were no significant differences in ETV group (P>0.05). Conclusion: MLT can enhance the antiviral effect of ETV in the HBV-infected mice, and the mechanism may be that MLT can cause the increase of Mg²⁺ contents in the CD8+ T cells to improve the activity of CD8+ T cells, and thereby HBV can be removed more effectively.

Key words: hepatitis B virus, magnesium-L-threonate, entecavir, CD8+ T cells