Changes Of PPARα On The Process Of Alcoholic Liver Disease In Rats

Objective: In recent years, incidence rate of liver disease(alcoholic liverdisease, ALD) has increased year by year due to the heavy drinking ofalcoholic for a long time. The initial pathological mainly changes arehepatocyte fatty degeneration, then progress to steatohepatitis, hepatic fibrosis,and finally lead to cirrhosis. Peroxisome proliferator activated receptor α(PPARα) are involved in all links of lipid catabolism, including fatty acidintracellular binding, the fatty acid transdermal absorption, lipoproteinsynthesis and transport, promoting the expression of carnitinepalmitoyltransterase(CPT) and the synthesis of fatty acyl coenzyme Asynthetase(ACS). So we speculated that PPARα may play an important rolein the pathogenesis of ALD. Therefore, ALD model was established byalcohol infusion for the observation of the PPARα, further to investigate thePPARα in the pathogenesis of ALD.Methods: Fifty healthy male Wistar rats were randomly divided intocontrol group(n=10) and model group(n=40). Alcohol infusion wasperformed at 9:00 every day in the model group(the concentration of ethanolis 30%-60%, 5-9g/kg/d) which continued for 4-16 weeks, 5 rats died duringthe experimental process because in alcohol infusion process we strayed intothe trachea lead to suffocation). we obtained the hepatic tissue respectively at4 th week(n=10), 8th week(n=9), 12 th week(n=8) and 16 th week(n=8), partof the tissue was fixed in 4% neutral formaldehyde solution, which were usedfor immunohistochemical staining; the remaining tissue frozen in liquidnitrogen, save in the-80℃ refrigerator, which were used for observation ofPPARα protein and m RNA detection.Results: Changes in PPARα expression: with the prolonged time ofethanol infusion, immunohistochemistry and Western-blot analysis showedthat, the expression of PPAR protein in liver tissue of model group ratsdecreased gradually, were significantly lower than the control group(P<0.05).Real time fluorescence quantitative polymerase chain reaction(RT-q PCR)results showed, with the prolonged time of ethanol infusion, the expression ofPPARα m RNA of hepatic tissue in model group decreased gradually, andsignificantly lower than the control group(P<0.05).Conclusions:1 The rat model of ALD was constructed successfully.2 With the time prolonging, PPARα activity decreased gradually in thepathogenesis of ALD, that suggesting PPARα was involved in the progress ofALD.