The Study Of The Expression And Degradation Of SREBPs In Liver By Ethnaol

Background:The incidence of alcoholic liver disease(ALD)in our country has increased markedly and alcohol becomes the second reason of hepatic lesion after virus hepatitis in these years.The classical clinical manifestations of ALD are alcoholic fatty liver(AFL), alcoholic hepatitis and alcoholic liver fibrosis,which even can become inconvertible alcoholic cirrhosis.So the prevention and cure of ALD become more and more important in medical topic.The study and research of ALD has increasingly increased in world,but most of them are concentrating on the direct toxic action to liver cell by alcohol itself or its metabolic product and the contribution by the changes of nutritional disturbance,liver metabolism abnormality and lipid peroxidation in ALD.Lipid metabolism disorder is the basis of AFL and is controled by sterol regulatory element-binding proteins(SREBPs)in molecular mechanism for the increasing of transcription of many enzymes related with lipid synthsis,such as acetyl CoA carboxylase(ACC)and fatty acid synthase(FAS).The mechanism of SREBPs in AFL has not been well known,and there is no report about the degradation of SREBPs all over the word.So,our investigation of the expression and the degradation of SREBPs in rat models of AFL is important and helpful for the deeper reseach on the AFL and the treatment of AFL.Objective:By setting up rat models of alcoholic fatty liver,to investigate the changes of triglycerides,SREBP-1c and ACC,and to evaluate the expressions of Fbw7αmRNA and protein,the phosphorylation and acetylation of SREBP-1c which affect the degradation of SREBP-1c.Methods:After one-week acclimatization period,30 male Wistar rats(180±10g)were divided into two groups:a normal control group and an alcoholic fatty liver model group(n=15).The rats in the model groups were gavaged by intragastric ethanol infusion,and the rats in the control group were treated with saline of the same volume.At the end of 12th week of the experiment,the rats were sacrificed.Liver histology was detected by HE staining and the parameters of triglyceride contents were measured by GPO-PAP assay.Samples of the liver were subjected to PCR or Western blot for the expressions of ACC,SREBP-1c,Fbw7αand immunoprecipitation studies for the phosphorylation and acetylation of SREBP-1c.Results:Pathology observation by light microscope showed liver steatosis in model group.The expression of TG,SREBP-1c,ACC in model group were dramatic higher than control group.Alcohol induced a decrease of Fbw7αmRNA,protein and the phosphorylation of SREBP-1c in the model group,which negatively correlated with the TG content,while increased SREBP-1c and its acetylation which positively correlated with the TG content.Conclusion:The higher SREBP-1c,ACC by the alcohol administration result in a increased fatty synthesis and TG to form the alcoholic fatty liver.And alcohol increased SREBP-1c not only by decreasing the Fbw7α,but also by decreasing the phosphorylation of SREBP-1c and increasing acetylation of SREBP-1c which cause the weaker interactions between SREBP-1c/Fbw7 and the poor degradation of SREBP-1c.