非酒精性脂肪肝的发病机制和治疗

Pathogenesis and treatment of non-alcoholic fatty liver disease

为进一步认识非酒精性脂肪肝(non-alcoholic fatty liver disease,NAFLD)的发病机制,寻求NAFLD临床最佳疗效依据,本文作者对近年来NAFLD的发病机制及治疗进行了归纳和分析整理,发现NAFLD与诸多因素有关,其中最为重要的是活性氧簇(reactive oxygen species,ROS)的产生,在两次打击中,以胰岛素抵抗为基础,ROS为中心环节,并在一系列相关因素如瘦素抵抗、caspase-3、Fas及其配体、外周血自然杀伤T细胞、环氧合酶2、代谢性核受体、肝细胞铁沉积、铁蛋白、结合珠蛋白、视黄醇结合蛋白4、肠道菌群失调、线粒体功能失调以及内质网压力的作用下,共同促进了NAFLD的进展。针对发病机制,临床治疗除常规改善胰岛素抵抗,抗氧化,改善脂质代谢外,还可采用核代谢配体或激活剂、铁螯合剂以及中医辨证论治方法。

In order to explore the pathogenesis of non-alcoholic fatty liver disease （NAFLD）, and to find the best evidence for clinical practice, recent literature about the pathogenesis and treatment of NAFLD was analyzed, and it was found that the generation of reactive oxygen species （ROS） is the most important factor in development of NAFLD. Based on insulin resistance （IR）, generation of ROS is a central link in the course of ＂two hits＂. Other factors, such as leptin resistance, caspase-3. Fas and its ligand, peripheral natural killer T cells, cyclooxygenase-2, metabolic nuclear receptors, hepatic deposition of iron, ferritin, haptoglo- bin, retinol binding protein 4, imbalance of intestinal flora, mitochondrial dysfunction and endoplasmic reticulum stress, also contribute to the progress of NAFLD. In the treatment of NAFLD, beside the conventionally used methods such as IR improvement, antioxidation and lipid metabolism improvement, other medicines such as nuclear metabolism ligands or activators, iron-chelating agents and syndrome differentiation treatment in traditional Chinese medicine also have good efficacy.