Protective effect of marein against alcoholic fatty liver and its mechanism
OBJECTIVE To explore the protective effect of marein against alcoholic fatty liver(AFL)and its potential mechanisms.METHODS AFL mice model was established with strong wine by gavage.The mice were randomly divided into normal control group(n=9,0.5%sodium carboxymethyl cellulose solution),model group(n=10,0.5%sodium carboxymethyl cellulose solution)and marein 75 and 150 mg/kg groups(n=9).Mice were given relevant medicine intragastrically,once a day,for consecutive 30 days.After the last medication,the levels of triglyceride(TG),malondialdehyde(MDA),and superoxide dismutase(SOD)in liver tissue were determined,and hepatic histopathological changes of liver tissue were observed;the protein expression levels of peroxisome proliferator-activated receptor α(PPARα),carnitine palmitoyltransferase-1(CPT-1),and diacylglycerol acyltransferase(DGAT)were determined in liver tissue.BRL hepatocytes injury model was induced by ethanol combined with ferrous sulfate and oleic acid;after treatment with 3,6 and 12 μmol/L of marein for 24 h,the distribution of lipid droplets,the levels of TG,MDA and SOD and protein expressions of PPARα,CPT-1 and DGAT in hepatocytes were examined.After pretreatment with MK886(PPARα inhibitor,10 μmol/L),modeled hepatocytes were treated with 12 μmol/L of marein for 24 h,and the protein expressions of PPARα,CPT-1 and DGAT were determined.RESULTS As the results showed in vivo,compared with the model group,after treatment with 75 and 150 mg/kg of marein,the degree of steatosis was significantly reduced,and the levels of TG and MDA and protein expression of DGAT were significantly decreased(P＜0.05 or P＜0.01);the levels of SOD,protein expressions of PPARα and CPT-1 were significantly increased(P＜0.05 or P＜0.01).As the results showed in vitro,after treatment with 3,6 and 12 μmol/L of marein,the lipid accumulation of hepatocytes was significantly inhibited,and the levels of TG and MDA,protein expression of DGAT were significantly decreased(P＜0.05 or P＜0.01),while the levels of SOD,protein expressions of PPARα and CPT-1 were significantly increased(P＜0.05 or P＜0.01).After MK886 pretreatment,the effects of marein on the above protein expressions were abolished.CONCLUSIONS Marein might exert a protective effect against AFL.The mechanisms might be related to inhibiting oxidative stress-mediated injury and improving PPARα-mediated lipid metabolism signaling pathway.
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