Effects of resveratrol on levels of ceramide via regulating miRNA-122 in treating non-alcoholic fatty liver disease / 中国病理生理杂志

ABSTRACT

AIM: To observe the therapeutical effects of resveratrol on non-alcoholic fatty liver disease and its potential mechanism.METHODS: Male C57BL/6J mice were fed with high-fat and high-cholesterol diet to established non alcoholic fatty liver disease model, and were administrated with resveratrol at doses of 80 mg/kg and 160 mg/kg.After 4-week treatment, the blood sample was collected for determination of total cholesterol (TC) and triglyceride (TG).The liver tissues were harvested for measuring the liver lipid content.The histopathological examination were conducted with hematoxylin and eosin staining.The ceramide levels in the liver tissues were detected by HPLC-MS.The microRNA (mi-RNA)-122 levels in the liver tissues were detected by real-time PCR.The protein levels of serine palmitoyltransferase (SPT) were determined by Western blot.The HepG2 cells were cultured and divided into 5 groups control group, model group (induced by 0.25 mmol/L oleic acid), model+resveratrol group (treated with 5 μmol/L resveratrol), miRNA-122 siRNA group and resveratrol+miRNA-122 siRNA group.Except control group, the cells in other groups were stimulated with oleic acid and incubated with respective drugs simultaneously for 24 h.The levels of TC, TG and ceramide in the cells of each group were measured.The protein levels of SPT in each group were determined by Western blot.RESULTS: In non-alcoholic fatty liver disease mice, resveratrol dose-dependently reduced the serum TC and TG levels, decreased the lipid deposition, the ceramide level and the SPT protein level, and increased the level of miRNA-122 in the liver tissues.In the in vitro study, compared with model group, resveratrol reduced the serum TC and TG levels, decreased the ceramide level, reduced the SPT protein level.Compared with control group, the levels of TC, TG and ceramide, and the protein expression of SPT were increased in miRNA-122 siRNA group.Compared with miRNA-122 siRNA group, no statistical difference of TC, TG, ceramide and protein expression of SPT in resveratrol combined miRNA-122 siRNA group was observed.CONCLUSION: Resveratrol significantly reduces lipid accumulation by reduction of miRNA-122 and ceramide levels, and decrease in SPT protein levels in the liver.