sigma-1受体在非酒精性脂肪性肝病中表达及意义-expression and significance of sigma - 1 receptor in nonalcoholic fatty liver disease.docxVIP

第三军医大学硕士学位论文 第三军医大学硕士学位论文 PAGE PAGE 3 Expression and Significance of Sigma-1 Receptor in Nonalcoholic Fatty Liver Disease Abstract Nonalcoholic fatty liver disease(NAFLD) is a spectrum of disease,which encompasses nonalcoholic fatty liver(NAFL),nonalcoholic steatohepatitis(NASH), NASH related fibrosis or cirrhosis,even related hepatic carcinoma caused mainly by metabolic factors which excludes alcohol abusing,hepatic virus or drugs.The ‘two-hit’ hypothesis is most widely accepted as the mechanism involved in the progress of NAFLD.The first hit indicates that abundant lipids such as triglyceriods(TG) accumulate in the cytoplasm caused by insulin resistance(IR).The second hit mainly includes oxidative stress.While recent research found out endoplasmic reticulum stress(ERS) could play an important role in NAFLD. Our previous study in vivo confirmed that ERS did exist and prolong in the whole progress of NAFLD,which indicates that ERS may contribute to NASH from NAFL.But how the lipids accumulation in hepatocyte triggers ERS is unknown.In another way,it is important to find out the way that lipotoxity initiates ERS. ER is quite an important organelle for lipid synthesis,and also for protein systhesis,calcium restoring.At the condition of hepatocyte steatosis,lipid droplets first form in ER and then bud off into the cytoplasm. Sigma-1R,a molecule predominantly expressed on the ER,involves in the budding process. Silencing of Sigma-1R could trap the lipid droplets in ER,leading to disruption of ER environment and progressive pathogenesis.All of these clues indicate that Sigma-1R may be a potential target hit by lipid accumulation.But there is no study to search for its relationship with NAFLD.So the current study aims to figure out the expression and the significance of Sigma-1R in NAFLD preliminarily. Methods： In vitro model of hepatocyte steatosis was established by adding sodium palmitate into the culuture medium. HepG2 strain cells was cultured in DMEM medium conta