Abstract: Objective: In order to investigate the effect of nattokinase on the alleviation of alcoholic liver injury and its immunomodulatory effect in rats. Methods: Male Wistar rats were randomly divided into five groups: normal control (intragastrically administered with normal saline), model (gavaged with Erguotou liquor (56% alcohol, V/V) at 6 mL/(kg·d mb) for the first week, at 8 mL/(kg·d mb) for the second week, at 10 mL/(kg·d mb) for the third week, and at 11 mL/(kg·d mb) for the fourth to the tenth week), nattokinase control (orally administered with 530.39 FU/(kg·d mb) nattokinase), nattokinase intervention (administered with 530.39 FU/(kg·d mb) nattokinase and alcohol), and diammonium glycyrrhizinate intervention (administered with 200 mg/(kg·d mb) diammonium glycyrrhizinate and alcohol). The same dose of alcohol was given to the latter two groups as that for the model group. The experiment lasted for 10 weeks. Morphological examination of liver tissue was performed by hematoxylin and eosin (H&E) staining, and the ultrastructure of liver cells was observed by transmission electron microscopy. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), glutamyl transpeptidase (GGT), and cholinesterase (CHE) activities were determined. The spleen index was calculated and the number of CD4+ and CD8+ T lymphocyte subsets and natural killer (NK) cells in the peripheral blood of rats was determined by flow cytometry. Results: The morphological structure of liver tissue and the ultrastructure of liver cells in the model group showed obvious pathological changes and damage, which were improved significantly after nattokinase and diammonium glycyrrihizinate intervention. Compared with the model group, the levels of serum ALT, AST and GGT decreased significantly (P < 0.05) whereas CHE increased in the nattokinase intervention and diammonium glycyrrhizinate intervention groups. Moreover, the spleen index and the percentage of CD3+CD4+ T cells and CD3+CD8+ T cells increased significantly (P < 0.05), and the percentage of TCRαβ+CD161a+ NK cell also rose in different degrees in the nattokinase intervention and diammonium glycyrrhizinate intervention groups. Conclusion: Nattokinase attenuates alcoholic liver injury in rats, likely by regulating the proportion of immune effector cells such as CD4+, CD8+ T and NK cells and enhancing immune function.

Key words: nattokinase, alcoholic liver injury, immunomodulation, CD4+ and CD8+ T lymphocytes, natural killer cells