3-Methyladenine ameliorates CCl4-induced liver fibrosis and gut microbiota in mice / 临床检验杂志

ABSTRACT

Objective@#To investigate the role of gut microbiota in the amelioration of liver fibrosis induced by CCl4 in mice by 3-methyladenine (3-MA). @*Methods@#Fifteen mice were randomly divided into normal control group, liver fibrosis group and 3-MA treatment group. The liver fibrosis model was established by injecting CCl4, and the mice in the 3-MA treatment group were injected 3-MA additionally from the third week onwards. After 8 weeks, all of the mice were sacrificed and their blood, liver tissue and fecal samples were collected to analyze serum ALT, AST, GGT levels, liver histopathology and gut microbiota. @*Results@#Compared with the liver fibrosis group, serum ALT and AST levels in 3-MA treatment group decreased obviously ([68.6±4.2] U/L vs [111.0±7.8] U/L, [179.0±12.9] U/L vs [253.2±26.7] U/L, P＜0.01), and the degree of hepatic histopathological changes was reduced. The intestinal flora in three groups were distinguished by principal coordinate analysis (PCoA) and non-metric multi-dimensional scaling (NMDS) analysis. Compared with the normal control group, there were decreased Alpha diversity of intestinal community, reduced significantly abundance of Lachnospiraceae, and increased obviously abundance of Actinobacteria and Desulfovibrionacea in the liver fibrosis group (P＜0.05). Compared with the liver fibrosis group, there were increased Alpha diversity of intestinal community, increased significantly abundance of Lachnospiraceae and Blautia, and reduced abundance of Bifidobacteriaceae in the 3-MA treatment group (P＜0.05). In addition, the abundance of Lactobacillaceae in the 3-MA treatment group was significantly higher than that in the normal control group (P＜0.05). @*Conclusion@#3-MA improves the liver fibrosis of mice induced by CCl4, and gut microbiota may play an active role in this process.