Effect of Vitamin E on the Expression of SIRT1 and PGC-1α in Mice with Nonalcoholic Fatty Liver Disease / 中国药学杂志

ABSTRACT

OBJECTIVE: To investigate the effect of vitamin E (Vit E) on the expression of SIRT1 and PGC-1α in mice with nonalcoholic fatty liver disease(NAFLD), and to explore its role in the resistance against the oxidative stress. METHODS: As animal models of NAFLD, Male C57BL/6 mice were fed with high-fat diets for 24 weeks, the model mice was administered Vit E (50 mg·kg-1·d-1) intragastrically for 18 weeks from 7th week of modeling.The pathological changes in liver were determined by HE and Masson staining. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) analyzed using automatic biochemical instrumentation. The levels of liver superoxide-dismutase (SOD) and MnSOD were tested by xanthine oxidase assay. Total content of malondialdehyde (MDA) in liver homogenate was tested by thiobarbituric acid (TBA) method. The mRNA and protein levels of silent mating type information regulation 2 homolog 1(SIRT1) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) were tested by Real-time PCR and immunohistochemistry assay respectively. RESULTS: Long-term high-fat diet induced NAFLD with the progression from liver steatosis, inflammatory response to fibrosis. The levels of serum ALT and AST in the rats of the NAFLD group were significantly higher than those of the normal group(P<0.05). The transcript and protein levels of liver SIRT1 and PGC-1α were significantly decreased compared with the normal group. The total contents of liver SOD and MnSOD were much lower than those of the normal group, while the MDA level increased significantly(P<0.05).The administration of Vit E to some extent reduced inflammation and fibrosis.After Vit E treatment, the levels of serum ALT and AST were significantly lower than those of the model group(P<0.01, P<0.05). The mRNA and protein levels of liver SIRT1 and PGC-1α became higher than those of the model group(P<0.05).Then liver SOD and MnSOD levels were significantly increased compared with the model group(P<0.05) while MDA content was reduced(P<0.05). CONCLUSION: Vitamin E corrects the imbalances of the oxidative and antioxidative system in mice models of high-fat diet-induced NAFLD by regulating the expression levels of the key factors of the SIRT1/PGC-1α signaling pathway, which reduces inflammation damage in liver and prevents the progression of NAFLD.