非酒精性脂肪性肝炎药物治疗的研究动态  

Research advances in drug treatment for nonalcoholic steatohepatitis

作　　者：袁平戈[1] YUAN Pingge(The Second Affiliated Hospital of Chongqing Medical University,Chongqing,400010)

机构地区：[1]重庆医科大学附属第二医院,重庆市400010

出　　处：《西南医科大学学报》2020年第2期107-113,共7页Journal of Southwest Medical University

摘　　要：非酒精性脂肪性肝病患病率不断增高,呈全球化、大众化、低龄化趋势。针对非酒精性脂肪性肝病发病机制的靶向干预是当前研究的热点,到2018年为止已发现190个治疗靶点。目前进入临床三期有6个,处于二期的30多个,处于一期的20多个。非酒精性脂肪性肝病的治疗药物有4个主要通路为靶点:(1)着眼于肝脏脂肪堆积和随之产生的代谢应激,包括:(1)过氧化物酶体增殖物-激活受体激动剂;(2)作用于胆汁酸-法尼醇X受体轴的药物;(3)脂肪从头合成抑制剂;(4)肠促胰素;(5)成纤维细胞生长因子等。(2)靶点为氧化应激、炎症、细胞损伤或凋亡的药物:(1)抗氧化剂;(2)作用于肿瘤坏死因子α通路的药物;(3)免疫调节剂等。(3)作用于肠道,或肠道微生态调节剂;(4)抗纤化药物等。全球在非酒精性脂肪性肝炎的新药研发领域投入巨大,但从目前临床试验结果来看,对非酒精性脂肪性肝炎患者的组织学改善,包括炎症和肝纤维化的改善效果并不十分理想。Nonalcoholic fatty liver disease,a more and more common disease worldwide,shows an increasingprevalence and a trend toward younger population.Interventions targeting the pathogenesis of nonalcoholic fatty liverdisease are the focus of current research.One hundred and ninety therapeutic targets have been found until 2018,with 6,30 plus,and 20 plus targets in phase III,II,and I clinical trials,respectively.There are four main path-ways targeted for the treatment of nonalcoholic fatty liver disease.(1)Drugs targeting liver fat accumulation and theresulting metabolic stress:peroxisome proliferator-activated receptor agonists,drugs acting on the bile acid-farne-soid X-receptor axis,inhibitors of de novo fat synthesis,incretins,fibroblast growth factors,etc.(2)Medicine tar-geting oxidative stress,inflammation,cell damage,or cell apoptosis:antioxidants,medicine acting on the tumor ne-crosis factor alpha pathway,immunomodulators,etc.(3)Intestinal microecological regulators.(4)Antifibrotics.Al-though a huge investment has been poured into new drug research for nonalcoholic steatohepatitis,current clinicaltrials have yet found a satisfactory way to improve the patients’histological indicators including inflammation andliver fibrosis.

关 键 词：脂肪肝 非酒精性 非酒精性脂肪性肝炎 治疗 药物 进展 

分 类 号：R575[医药卫生—消化系统]