To investigate the effects ofS-Adenosylmethionine(SAM)on liver injury induced by carbon tetrachloride(CCl4)in mice,In this study,60 C57BL/6 mice were randomly divided into CON group,CCl4 group,low dose group(CCl4+SAM-L,50 mg/kg SAM),medium dose group(CCl4+SAM-M,100 mg/kg)and high dose group(CCl4+SAM-M,200 mg/kg).Except CON group,mice in other groups were intraperitoneally injected with CCl4(10 mL/kg,0.2％),and mice in CON group were injected with equal volume olive oil,3 times a week for 4 weeks,to establish mouse liver injury model.At the same time,mice in low,medium and high dose groups were given 100 μL SAM,CON group and CCl4 group were given equal volume PBS for 4 weeks.The results showed that CCl4 promoted liver fibrosis and increased serum ALT,AST and TBIL levels(P＜0.05).Different doses of SAM significantly alleviated liver fibrosis injury and decreased serum ALT,AST and TBIL levels(P＜0.05).Compared with CON group,CCl4 significantly decreased the liver T-AOC,SOD,CAT and GSH-Px levels(P＜0.05),and increased the liver MDA level(P＜0.05).Compared with CCl4 group,the levels of T-AOC,SOD,CAT and GSH-PX in liver of mice in CCl4+SAM group were significantly increased(P＜0.05),while the level of MDA was significantly decreased(P＜0.05).Compared with CON group,liver levels of IL-6,IL-1β and TNF-α in CCl4 group were significantly increased(P＜0.05).Compared with CCl4 group,different doses of SAM could significantly reduce the levels of IL-6,IL-1β and TNF-α in liver of mice(P＜0.05).Compared with CON group,the expressions of Nrf2,NQO-1 and HO-1 genes in liver of CCl4 group were decreased(P＞0.05),while the expression of Keap1 gene was significantly increased(P＞0.05).Compared with CCl4 group,medium and high doses of SAM significantly increased the expressions of Nrf2,NQO-1 and HO-1 genes in liver of mice(P＜0.05),and decreased the expres-sion of Keap1 gene(P＞0.05).Compared with CON group,the contents of acetic acid,propionic acid and butyric acid in cecum of CCl4 group were significantly decreased(P＜0.05).Compared with CCl4 group,the contents of propionic acid and butyric acid in high-dose SAM group were sig-nificantly increased(P＜0.05).Microbial analysis showed that CCl4 significantly decreased the rel-ative abundance of Akkermansia and Prevotellaceae_NK3B31_group(P＜0.05),and changed the composition of intestinal microorganisms.These results indicate that SAM regulates the gene ex-pression of Nrf2 antioxidant signaling pathway to a certain extent,increases intestinal SCFAs con-tent,regulates intestinal microbial structure,and thus alleviates liver injury,oxidative stress and inflammation caused by CCl4.This study provides reference and theoretical basis for SAM in the treatment and remission of drug-induced liver injury.

To investigate the effects ofS-Adenosylmethionine(SAM)on liver injury induced by carbon tetrachloride(CCl4)in mice,In this study,60 C57BL/6 mice were randomly divided into CON group,CCl4 group,low dose group(CCl4+SAM-L,50 mg/kg SAM),medium dose group(CCl4+SAM-M,100 mg/kg)and high dose group(CCl4+SAM-M,200 mg/kg).Except CON group,mice in other groups were intraperitoneally injected with CCl4(10 mL/kg,0.2％),and mice in CON group were injected with equal volume olive oil,3 times a week for 4 weeks,to establish mouse liver injury model.At the same time,mice in low,medium and high dose groups were given 100 μL SAM,CON group and CCl4 group were given equal volume PBS for 4 weeks.The results showed that CCl4 promoted liver fibrosis and increased serum ALT,AST and TBIL levels(P＜0.05).Different doses of SAM significantly alleviated liver fibrosis injury and decreased serum ALT,AST and TBIL levels(P＜0.05).Compared with CON group,CCl4 significantly decreased the liver T-AOC,SOD,CAT and GSH-Px levels(P＜0.05),and increased the liver MDA level(P＜0.05).Compared with CCl4 group,the levels of T-AOC,SOD,CAT and GSH-PX in liver of mice in CCl4+SAM group were significantly increased(P＜0.05),while the level of MDA was significantly decreased(P＜0.05).Compared with CON group,liver levels of IL-6,IL-1β and TNF-α in CCl4 group were significantly increased(P＜0.05).Compared with CCl4 group,different doses of SAM could significantly reduce the levels of IL-6,IL-1β and TNF-α in liver of mice(P＜0.05).Compared with CON group,the expressions of Nrf2,NQO-1 and HO-1 genes in liver of CCl4 group were decreased(P＞0.05),while the expression of Keap1 gene was significantly increased(P＞0.05).Compared with CCl4 group,medium and high doses of SAM significantly increased the expressions of Nrf2,NQO-1 and HO-1 genes in liver of mice(P＜0.05),and decreased the expres-sion of Keap1 gene(P＞0.05).Compared with CON group,the contents of acetic acid,propionic acid and butyric acid in cecum of CCl4 group were significantly decreased(P＜0.05).Compared with CCl4 group,the contents of propionic acid and butyric acid in high-dose SAM group were sig-nificantly increased(P＜0.05).Microbial analysis showed that CCl4 significantly decreased the rel-ative abundance of Akkermansia and Prevotellaceae_NK3B31_group(P＜0.05),and changed the composition of intestinal microorganisms.These results indicate that SAM regulates the gene ex-pression of Nrf2 antioxidant signaling pathway to a certain extent,increases intestinal SCFAs con-tent,regulates intestinal microbial structure,and thus alleviates liver injury,oxidative stress and inflammation caused by CCl4.This study provides reference and theoretical basis for SAM in the treatment and remission of drug-induced liver injury.