FXR激动剂在非酒精性脂肪性肝炎治疗中的研究进展

Research progress of FXR agonists in the treatment of nonalcoholic steatohepatitis

非酒精性脂肪性肝炎(Non-alcoholic steatohepatitis,NASH),又称代谢性脂肪性肝炎,是病理变化与酒精性肝炎相似但无过量饮酒史的临床综合征,好发于中年特别是超重肥胖个体。非酒精性脂肪性肝炎与肥胖、胰岛素抵抗、2型糖尿病、高脂血症等代谢紊乱关系密切,主要特征为肝细胞大泡性脂肪变伴肝细胞损伤和炎症,严重者可发展为肝硬化,但至今NASH尚无得到批准的治疗方案。在寻找有效的治疗方法时,解决代谢失调、炎症和抗纤维化的新策略不断涌现。法尼类X受体(Farnesoid X receptor,FXR)除了是胆汁酸代谢和肠肝循环的关键调节剂外,还参与调节代谢稳态,使其成为NASH中有吸引力的治疗靶点。本文综述了FXR激动剂对NASH治疗的研究进展。

Non-alcoholic steatohepatitis(NASH),also known as metabolic steatohepatitis,is a clinical syndrome with pathological changes similar to alcoholic hepatitis but without history of excessive drinking,likely to occur in the middle-aged,especially overweight and obese individuals.Nonalcoholic steatohepatitis is closely related to obesity,insulin resistance,type 2 diabetes,hyperlipidemia and other metabolic disorders.Its main feature is hepatocyte vesicular steatosis with hepatocyte injury and inflammation.Severe cases can develop into liver cirrhosis,but so far there is no approved treatment for NASH.In the search for effective treatments,new strategies to address metabolic disorders,inflammation and antifibrosis are constantly emerging.Besides being a key regulator of bile acid metabolism and enterohepatic circulation,farnesoid X receptor(FXR)is also involved in regulating metabolic homeostasis,making it an attractive therapeutic target in NASH.This article reviews the progress and prospect of FXR agonists in the treatment of NASH.