SIRT3与非酒精性脂肪性肝病肝细胞脂肪变性关系的临床研究

背景：非酒精性脂肪性肝病（NAFLD）是指在多种因素的共同作用下，肝细胞逐渐发生脂肪变性的临床病理过程。SIRT3与棕色脂肪的产热有关，肝细胞内可检测到其表达。目的：通过检测NAFLD患者肝活检标本中SIRT3、AMP活化蛋白激酶（AMPK）、乙酰辅酶A羧化酶1（ACC1）和同醇调节元件结合蛋白-1（SREBP—1）的表达，探讨SIRT3与NAFLD肝细胞脂肪变性的关系。方法：从体检人员和部分行肝胆外科手术者中纳入56例NAFLD患者，12例健康体检者作为对照组。受试者先以超声检查初步诊断脂肪肝程度，然后行肝穿刺活检，确定组织病理学肝细胞脂肪变性程度，以免疫组化方法检测SIRT3、AMPK、ACC1、SREBP-1表达。结果：超声诊断的脂肪肝分级与组织病理学肝细胞脂肪变性程度一致。脂肪肝患者肝细胞内SIRT3和AMPK表达量显著低于对照组（P〈0．05），并随脂肪肝程度的加重而减低；ACC1和SREBP．1表达量显著高于对照组（P〈0．05），并随脂肪肝程度的加重而增加。结论：SIRT3与NAFLD的肝细胞脂肪变性呈负相关．其表达降低可能通过下调AMPK表达，使脂肪合成基因ACC1和SREBP-1表达增加，导致肝细胞发生脂肪变性。

Clinical Investigation of Relationship between SIRT3 and Hepatocyte Steatosis in Nonalcoholic Fatty Liver Disease

Background： Nonalcoholic fatty liver disease （NAFLD） is a gradually developed elinieopathologie process of hepatoeyte steatosis under the jointly role of multiple factors. SIRT3 plays an important role in the thermogenesis of brown adipose, and can be identified in hepatocytes. Aims： To investigate the expressions of SIRT3, AMP-activated protein kinase （AMPK）, aeetyl CoA carboxylase 1 （ACC1） and sterol regulatory element binding protein-1 （SREBP-1） in liver biopsy specimens from patients with NAFLD, and to explore the relationship between SIRT3 and hepatocyte steatosis in NAFLD. Methods： Fifty-six NAFLD patients were selected from a population underwent health examination and patients received hepato-biliary surgery, 12 healthy people were served as controls. The degree of fatty liver was staged by ultrasonography, and then the histopathologie severity of hepatocyte steatosis was identified in liver biopsy specimens from the NAFLD and controls. The expression levels of SIRT3, AMPK, ACC1 and SREBP-1 were determined by immunohistoehemistry. Results： The degree of fatty liver staged by ultrasonography was in concordance with the severity of hepatocyte steatosis identified histopathologically. The expression levels of SIRT3 and AMPK were significantly lower in hepatoeytes of fatty liver patients than those of the controls （P〈0.05）, the levels decreased in parallel with the aggravation of fatty liver; whereas the expression levels of ACC1 and SREBP-1 were significantly higher in hepatoeytes of fatty liver patients than those of the controls （P〈0.05）, the levels increased in parallel with the aggravation of fatty liver. Conclusions： SIRT3 is negatively correlated with the hepatocyte steatosis in NAFLD. Down-regulation of SIRT3 might be involved in hepatoeyte steatosis via down-regulation of AMPK and up-regulation of adipose synthesis-associated genes such as ACC1 and SREBP-1.