Regulation of SIRT3/FOXO1 Signaling Pathway in Rats with Non-alcoholic Steatohepatitis by Salvianolic Acid B.

AIMS: To explore the effect of salvianolic acid B (Sal B) on regulation of SIRT3/FOXO1 signaling pathway in rats with non-alcoholic steatohepatitis (NASH).

METHODS: Sixty Sprague Dawley (SD) rats were randomly divided into control, model and treatment groups. After 12 weeks of successful model establishment with high fat diet, treatment group was given Sal B by intragastric administration. After 12 weeks of treatment, rats were sacrificed and livers were taken to test indicators such as liver index, TG, TC, ALT, AST, reactive oxygen species (ROS) by DCFH-DA probe, SOD2 activity by WST-8 test. mRNA and protein expression of SIRT3, SOD2, catalase were detected by real time PCR and western blot, respectively. The acetylation level of FOXO1 and SOD2 was detected by immuno-precipitation (IP).

RESULT: Liver index, ALT, AST, TG, TC, and ROS of model group were higher than those of control and treatment groups, which the difference was statistically significant (p <0.01). SOD2 activity of model group was lower than that of control and treatment groups. In treatment group, HE staining and electron microscopy showed hepatic tissue pathological change and mitochondrial structure damage alleviate. mRNA and protein expression of SIRT3, SOD2, catalase were lower in model group and the difference was statistically significant (p <0.05), which was opposite in the acetylation level of FOXO1 and SOD2 by IP.

CONCLUSION: Sal B can decrease oxidative stress reaction by regulating SIRT3/FOXO1 signaling pathway and play a therapeutic role in the treatment of NASH in rats.