摘要
目前,非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)已经成为全球性的慢性肝脏疾病,其较高的发病率与肥胖症、糖尿病及代谢紊乱等密切相关.伴随促炎症反应和肝纤维化而发生的胰岛素耐受、脂质代谢紊乱是NAFLD进一步恶化的标志.核受体法尼酯衍生物X受体(farnesoid X receptor,F X R)对脂类的代谢和体内平衡过程具有重要的调节作用,对其功能特性的深入研究,可为非酒精性脂肪性肝炎(non-alcoholic steatohepatitis,NASH)的病理生理学特征提供更深的认识,并阐明NAFLD/NASH潜在药物治疗靶点的机制.FXR的激活可以抑制肝脏脂肪的从头合成,增加胰岛素的敏感性以及避免胆汁酸诱导的细胞毒性.结合临床研究提示,FXR的激动剂或调节剂有望用来治疗NAFLD和NASH类肝脏疾病.本文着重对FXR在NASH中的重要调节作用作一综述.
Non-alcoholic fatty liver disease（NAFLD） has become a very common chronic liver disease all over the world. The high incidence of NAFLD is closely related to obesity, diabetes and metabolic disorders. Insulin resistance and dyslipidemia following the hepatic proinflammatory response and fibrosis are the primary features of NAFLD deterioration. Nuclear receptor farnesoid X receptor（FXR） regulates lipid metabolism and homeostasis. Clarification of FXR function and features can provide a better understanding of the pathophysiological characteristics of nonalcoholic steatohepatitis（NASH） and illuminate the mechanism of NAFLD/NASH potential therapeutic targets. FXR activation can inhibit the de novo hepatic lipogenesis, improve insulin sensitivity and protect against bile acid-induced cytotoxicity. Clinical studies indicated that FXR agonists or modulators are very promising for the clinical treatment of NAFLD and NASH. This review focuses on the important regulatory role of FXR in NASH.
出处
《世界华人消化杂志》
CAS
2016年第15期2289-2297,共9页
World Chinese Journal of Digestology
基金
国家自然科学基金资助项目
Nos.81273580
81473280
81302826
辽宁省重点实验室基金资助项目
No.LZ2015027~~
