胆汁酸核受体FXR在非酒精性脂肪性肝病中的作用

Role of farnesoid X receptor in nonalcoholic fatty liver disease

非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)是以肝细胞脂肪变性和脂质沉积为特征,但无过量饮酒史、排外病毒感染和其他原因引起的肝脏疾病.NAFLD已成为一个全球关注的健康问题,其发病机制仍未阐明,尚无有效的药物治疗手段.法尼醇X受体(farnesoid X receptor,FXR)是需配体激活的转录因子,在胆汁酸、糖脂代谢中起着重要的调节作用.近年来研究显示FXR参与调控胰岛素抵抗(insulin resistance,I R)、脂质代谢异常、抑制肝星状细胞活化及炎症细胞渗入、促进肝内循环及肝细胞再生、延缓肝纤维化进程等NAFLD的重要环节.动物实验和临床研究也证实,FXR激动剂有延缓、治疗NAFLD的作用.提示FXR可能是NAFLD的潜在治疗靶点.目前,FXR应用于NAFLD仍存有争议.

Nonalcoholic fatty liver disease（NAFLD） is characterized by the aberrant accumulation of triglycerides in hepatocytes in the absence of significant alcohol consumption, viral infection or other specific causes of liver disease. NAFLD has become a global health problem, but its pathogenesis remains poorly understood and no efficient pharmaceuticaltreatments have yet been established. The farnesoid X receptor（FXR） is a member of nuclear receptors of intracellular ligandactivated transcription factors and plays an important role in metabolism of bile acids, lipid and glucose. In addition, it has been recently reported that FXR participates in regulating insulin resistance and lipid metabolic disorder, inhibiting the activation of hepatic stellate cells and penetration of inflammatory cells, and promoting the enterohepatic circulation and regeneration of liver cells to defer liver fibrosis, which is significant for NAFLD. Several FXR agonists have been identified and proved to be optimistic in preventing and treating NAFLD both experimentally and clinically, indicating that FXR may be a therapeutic target for NAFLD. The use of FXR in NAFLD remains controversial currently.