Abstract: Objective To study the changes in the distribution of intrahepatic macrophages and lymphocytes in the mouse model of hepatic fibrosis induced by carbon tetrachloride(CCl4). Methods The hepatic fibrosis model was established in C57BL/6 mice by intraperitoneal injection of CCl4. The degree of hepatic fibrosis was evaluated by hematine-eosin and Masson staining. The peripheral serum of mice was collected to detect liver function index and blood lipid level. The distribution of hepatic immune cell subsets in liver mononuclear cells were analyzed using multi-color flow cytometry. Results Levels of serum alanine transaminase, aspartate aminotransferase, triglyceride and high density lipoprotein cholesterol were significantly higher in CCl4 group than those in control group. CCl4 group had advanced fibrosis(stage 3-4) according to Metavir score. The percentage of Kupffer cells in CCl4 group(13.33±1.91%) was significantly higher than that in control group(8.17±2.00%), in which the percentage of M1 phenotype Kupffer cells with CD11c+ marker increased significantly while the percentage of M2 phenotype Kupffer cells with CD206+ marker had no significant difference. The proportions of T cells and natural killer T(NKT) cells in CCl4 group were significantly lower than those in control group(20.17±4.07% vs. 36.00±4.61%, 8.71±1.37% vs. 23.41±3.38%). While there was no significant difference in the proportions of NK cells and B cells between the 2 groups. Conclusion In CCl4-induced hepatic fibrosis model, the increase of Kupffer cells in liver was mainly caused by M1 macrophages with pro-inflammatory effect, while the proportions of NKT cells and T cells were significantly decreased. The role of M1 macrophages in the development of liver fibrosis needs to be further explored.

Key words: Hepatic fibrosis, Flow cytometry, Macrophage, Lymphocyte