非酒精性脂肪性肝病的肝靶向治疗研究进展

Research progress in liver targeted therapy for nonalcoholic fatty liver disease

非酒精性脂肪性肝病(NAFLD)是最常见的进行性疾病,临床上目前尚无疗效确切的治疗药物。介绍了脂肪酸-胆酸偶合物(FABACs)和熊去氧胆酸-溶血磷脂酰乙醇胺偶合物(UDCA-LPE)两种新型的具有NAFLD防治作用的肝靶向药物的研究进展。FABACs通过调节脂代谢,特异性的降低高脂饲料所致NAFLD的肝脏脂肪升高,预防NAFLD的形成;而且对已形成的NAFLD也有治疗作用;Ⅱ期临床研究结果显示其起效快、安全性好。UDCA-LPE在降低NAFLD的肝脏脂肪的同时,能够抑制线粒体损伤和凋亡,促进肝细胞再生,对NAFLD发展过程中的相关炎症具有显著的抑制作用。因此,FABACs和UDCA-LPE对防治NAFLD具有良好的应用前景。

Nonalcoholic fatty liver disease （NAFLD）is the most common progressive liver disease worldwide.Currently,there is no satisfying treatment for NAFLD.Research progress in fatty acid bile acid conjugates （FABACs）and ursodeoxycholyl lysophosphatidylethanolamide （UDCA-LPE）,which are two novel liver targeted drugs with anti-NAFLD effects,is reviewed.FABACs,which reduce liver fat in patients with NAFLD induced by high-fat diet by regulating lipid metabolism,have been proved effective in preventing and treating NAFLD. The safety and efficacy of FABACs in NAFLD patients have been confirmed in a phase II,randomized,double-blind,placebo-controlled trial.UDCA-LPE can not only reduce liver fat in NAFLD patients,but also inhibit mitochondrial damage and apoptosis and promote hepatocyte regeneration,with a marked anti-inflammatory effect during the development of NAFLD.Therefore,FABACs and UDCA-LPE hold promise for preventing and treating NAFLD.