Résumé
Aim To study the effects of naringenin on MCD diet-induced liver fibrosis and its related mechanisms.Methods LX2 cells were incubated with TGF-β1 for 24 h to establish the in vitro fibrosis model.LX2 cells were treated with NGN at the same time.Male C57BL/6 mice were fed with MCD diet for six weeks to induce liver fibrosis.100 mg·kg-1·d-1 NGN was administered by gavage simultaneously.The protein expressions of α-SMA, col1, TGF-β1, p-smad2 and p-smad3 were evaluated by Western blot.The mRNA expressions of α-SMA, col1 and col3 were detected by qRT-PCR.The degree of liver fibrosis was evaluated by Sirius red staining.Results Both in in vivo and in vitro experiments, compared with model group, the mRNA levels of α-SMA, col1 and col3 and protein levels of α-SMA, TGF-β1, p-smad2 and p-smad3 significantly decreased in NGN treatment group.The results of HE staining and Sirius red staining also indicated that NGN significantly decreased liver fibrosis induced by MCD diet.Conclusions Naringin can significantly inhibit liver fibrosis induced by MCD diet, which may be related to TGF-β1/Smad pathway.
Résumé
OBJECTIVE The pathological characteristics of nonalcoholic steatohepatitis (NASH) include liver steato?sis, inflammation, and fibrosis. Fibrosis is the most severe and significant pathological feature in NASH. Effective drug treatment could reverse early liver fibrosis and is of significance to prevent NASH from progressing into cirrhosis and liver cancer. Identification of drug targets for NASH treatment has been an active research area and is essential for the development of anti-NASH medications. Naringenin (NGN) is a flavonoid compound rich in citrus fruits. Our preliminary data demonstrated that NGN reduced diet-induced lipid accumulation and inflammation in the mouse liver, but whether NGN can attenuate liver fibrosis of NASH is not known. METHODS To study the effect of NGN on NASH fibrosis. WT mice were fed with high fat diet (HFD) and injected intraperitoneally 20％ carbon tetrachloride at the same time for 8 weeks to induce NASH, and NGN was administrated by gavage in the meantime. In vitro, LO2 cells and LX2 cells were stimulated by oleic acid (OA) combined with lipopolysaccharide (LPS), respectively. RESULTS Treating the WT mice with NGN 100 mg · kg-1 · d-1 significantly attenuated hepatic lipid accumulation, hepatic fibrosis, plasma ALT and AST levels, inhibited protein expression of p-ERK, p-FoxO3a in the mouse livers. In vitro, on OA and LPS stimulated LO2 or LX2 cells, NGN significantly promoted apoptosis of activated hepatic stellate cells while inhibited apoptosis of hepatocytes. Mechanism study indicated that NGN inhibited MAPK pathway and promoted activation of FoxO3a, conse?quently promoted apoptosis of the activated LX2 cells and inhibited liver fibrosis. CONCLUSION NGN preventes NASH fibrosis via regulating MAPK/FoxO3a pathway, thus promoting apoptosis of the activated hepatic stellate cells.