ABSTRACT
Objective To investigate the molecular biological mechanism of deposition of triglyceride(TG)in hepatocytes in alcoholic fatty liver disease(AFLD)and the pathogenesis of this condition by detecting the contents of serum tumor necrosis fac-tor-α(TNF-α),liver triglyceride(TG),peroxisome proliferator-activated receptorα(PPARα)and acyl-CoA oxidase(Acox1)mR-NAs,and liver PPARαprotein after intervention with bezafibrate,a PPARαagonist.Methods Sixty Wistar rats were randomly divided into three groups:control group(n=20),AFLD group(n=20),and bezafibrate group(n=20).Animals in control group were given distilled water by gavage once a day for 8 weeks.Those in AFLD group were given ethanol and fish oil(2.5 mL/kg) by gavage daily for the same period of time.In bezafibrate group,rats were treated by gavage with ethanol and fish oil(2.5 mL/kg)for the first 4 weeks and then with bezafibrate(100 mg/kg)for another 4 weeks.TG in the liver was measured by colorimet-ric method,serum TNF-αlevels by enzyme linked immunoabsorbent assay (ELISA),the mRNA expression of PPARαand Acox1 in hepatocytes by reverse transcription polymerase chain reaction(RT-PCR)and the expression of PPARαprotein in hep-atocytes by Western blot.Results A significant increase in TG[AFLD group(0.72±0.09)mmol/L vs.control group(0.28± 0.07)mmol/L,P<0.01]and TNF-α[AFLD group(3.01±0.31)ng/mL vs.control group(1.07±0.28)ng/mL,P<0.01]was found in AFLD group when compared with control group.After bezafibrate intervention,the contents of liver TG and serum TNF-αwere significantly decreased.The mRNA expression of PPARα[AFLD group(0.22±0.08)vs.control group(0.68± 0.13),P<0.01]and Acox1[AFLD group(0.43±0.12)vs.control group(1.14±0.21),P<0.01]was suppressed in AFLD group,which was significantly reversed by bezafibrate treatment[bezafibrate group(0.59±0.13)for PPARαmRNA vs.AFLD group,P<0.01;bezafibrate group(0.83±0.17)for Acox1 mRNA vs.AFLD group,P<0.01].The expression of PPARαpro-tein in hepatocyts was also found to decrease in AFLD group[AFLD group(0.19±0.07)vs.control group(0.48±0.11),P<0.01].After bezafibrate intervention,it was profoundly increased.Conclusion The down-expression of PPARαand Acox1 in the liver of rats with AFLD may suppress the fatty acid metabolism and lead to the TG deposition in the liver.The increase in serum TNF-αcontents also contributes to the development of AFL.Bezafibrate can prevent and treat AFL by activating PPARα,increasing the expression of PPARαand Acox1 ,promoting the metabolism of fatty acids,decreasing the TG deposition and the serum TNF-αcontents.