非酒精性脂肪肝发病机制和治疗的研究进展

非酒精性脂肪性肝病(non-alcoholic fatty liver disease, NAFLD)已成为全球最常见肝病之一,其发病率仍然有继续增加的趋势。NAFLD是一类包含单纯性脂肪肝、非酒精性脂肪性肝炎(non-alcoholic steatohepatitis, NASH)等疾病的临床病理综合征,并可能进一步进展为肝硬化、肝衰竭和肝细胞性肝癌,威胁人类健康。目前NAFLD的发病机制尚不完全清楚,并且尚没有理想的有效治疗药物。该文主要就NAFLD的发病机制和治疗的研究进展进行综述,为NAFLD的基础研究和临床治疗提供相关的参考。     

益生菌改善非酒精性脂肪肝病的研究进展

非酒精性脂肪肝病(non-alcoholic fatty liver disease,NAFLD)是一种较为常见的慢性肝病,在我国居民中NAFLD正呈现低龄化和迅速上升的态势。而NAFLD的发病机制尚未完全阐明,一般认为其与肥胖、糖尿病、高脂血症、胰岛素抵抗及遗传易感等诸多因素相关。"肠-肝轴"学说的提出,使医药界同仁普遍认识到肠道益生菌在NAFLD的发生过程中扮演着重要角色,也随之引发了关于肠道益生菌对NAFLD治疗价值的思考与探索。该综述主要对益生菌改善NAFLD的研究进展进行总结,以期能够为NAFLD临床治疗提供参考。     

非酒精性脂肪性肝病诊断方法研究进展

非酒精性脂肪性肝病(non-alcoholic fatty liver disease, NAFLD)是一类进行性的慢性肝脏疾病,包括简单的脂肪蓄积、非酒精性脂肪性肝炎、进展性的肝纤维化、肝硬化和肝细胞肝癌。NAFLD具有致病机制复杂、疾病进行性、高发病率、伴随并发症风险以及无特效药物治疗等特征,这凸显出对NAFLD的发病机制认知、筛查、诊断与监测的重要性。因此,该文旨在介绍NAFLD的概况,着重从肝穿刺组织活检、影像学检查和血液标志物三个方面归纳与总结诊断方法的研究进展,为NAFLD的基础研究、临床诊断及其新的生物标志物研究提供相关的参考。     

Kupffer细胞在非酒精性脂肪肝病中的作用

非酒精性脂肪性肝病(non-alcoholic fatty liver disease, NAFLD)是一种无过量饮酒史、以肝细胞脂肪变性和脂肪贮积为特征的临床病理综合征。Kupffer细胞是位于肝脏中的特殊巨噬细胞,是先天免疫中的重要组成部分,在肝脏疾病中起关键作用。多项研究表明,Kupffer细胞在NAFLD的发生发展过程中起重要作用。本文总结了Kuffer细胞在NAFLD疾病发生发展中的多重作用,旨在为NAFLD的治疗提供一个有效的靶点。     

非酒精性脂肪性肝病的发病机制及治疗进展

近年来,随着人们生活水平的提高,脂肪性肝病的发病率明显上升,且患病年龄趋于低龄化,已经成为严重危害我国人民健康的常见疾病,我国非酒精性脂肪性肝病的发病率明显高于酒精性脂肪性肝病。本文主要对NAFLD的发病机制及相关治疗进展做简要的综述。NAFLD的发病机制与胰岛素抵抗、氧化应激、代谢综合征、脂肪细胞因子的作用、内质网应激、及铁超载等多种因素有关。NAFLD的治疗可以从防治原发病或相关危险因素、基础治疗(行为或生活方式干预;调整饮食;运动疗法)、药物治疗以及手术治疗等方面进行。了解国际上NAFLD的发病机制以及相关治疗进展,对遏制非酒精性脂肪性肝病的发生、发展趋势有着十分重要的意义。     

中药单体活性成分抗结直肠癌的研究进展

结直肠癌是消化道频发的重大恶性肿瘤,其发病率和致死率逐年攀升,严重威胁着人类生命安全。虽然多种化疗药物已广泛应用于临床,然而其潜在的毒副作用和耐药性致使患者依从性差,进而导致化疗以失败告终。基于此,亟待挖掘高效低毒的抗结直肠癌药物以应对现实的临床治疗窘境。中药单体成分作为中药发挥药效的主要效应物质,在临床抗结直肠癌方面优势凸显。与合成类化学制剂相比,其来源丰富,安全性高,在结直肠癌防治方面呈现出较大潜力。因此,本文从化学活性物质角度出发,系统总结了中药单体活性成分的抗结直肠癌作用和主要分子机制,并结合当前研究现状对中药治疗结直肠癌的相关研究进行了初步探讨,以期为中药单体成分抗结直肠癌研究及临床应用提供理论依据和参考价值。     

天然药物对非酒精性脂肪肝的作用

非酒精性脂肪性肝病(nonalcoholic fatty liver disease, NAFLD)是世界上最常见的慢性肝病,是由环境、遗传背景以及代谢应激之间相互作用产生的多因素疾病。所涉及到的机制复杂,目前已经证实的治疗NAFLD最有效的方法是,饮食干预和锻炼以减轻体重,尚未有专门用于治疗NAFLD的药物。大量的体内外实验证实,多种天然药物可以通过各种机制来干预NAFLD,且疗效显著。本文主要总结了近年来常用天然药物防治NAFLD的研究进展,为进一步的新药研发提供信息。     

中医药治疗溃疡性结肠炎的研究近况

正溃疡性结肠炎(ulcerative coliti,UC)是一种病因不明的慢性疾病,也是一种世界性的难治疾病[1]。该病以腹泻、腹痛、黏液脓血便、里急后重为主要临床表现,复发率高,治愈难度大,临床上西医治疗无特效手段。近年来,中医药在治疗UC方面进行了大量的研究,取得了较好的疗效,现就中医药治疗该病的研究近况综述如下。1中医对溃疡性结肠炎的认识中医古典书籍中并无慢性溃疡性结肠炎病名[2],归属于     

固醇调节元件结合蛋白2信号通路与非酒精性脂肪性肝病北大核心CSCD

非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)是以肝细胞内甘油三酯和胆固醇等脂毒性脂肪过度沉积为主要特征的一种临床获得性代谢综合征。最新研究表明,NAFLD向非酒精性脂肪肝炎(NASH)进展时,肝内胆固醇积累可能较甘油三酯更具有细胞毒性风险。固醇调节元件结合蛋白2(sterol regulatory element-binding protein 2,SREBP2)是脂质代谢重要的核转录因子之一,主要调控胆固醇的生物合成和体内平衡。SREBP2及其靶基因调控的胆固醇异常是引起非酒精性脂肪肝病发生发展的重要因素之一。因此,认识SREBP2信号通路中,上下游各因素的表达调控作用与NAFLD发病机制之间关系,就显得非常重要。本文总结了受SREBP2调控表达的靶基因的特点,着重介绍SREBP2调控胆固醇体内合成与平衡的信号通路与NAFLD发病机制之间关系,为研究和指导治疗NAFLD及其代谢性疾病提供新的思路。     

固醇调节元件结合蛋白2信号通路与非酒精性脂肪性肝病

非酒精性脂肪性肝病（non-alcoholic fatty liver disease,NAFLD）是以肝细胞内甘油三酯和胆固醇等脂毒性脂肪过度沉积为主要特征的一种临床获得性代谢综合征。最新研究表明,NAFLD向非酒精性脂肪肝炎(NASH)进展时,肝内胆固醇积累可能较甘油三酯更具有细胞毒性风险。固醇调节元件结合蛋白2（sterol regulatory element-binding protein 2,SREBP2）是脂质代谢重要的核转录因子之一,主要调控胆固醇的生物合成和体内平衡。SREBP2及其靶基因调控的胆固醇异常是引起非酒精性脂肪肝病发生发展的重要因素之一。因此,认识SREBP2信号通路中,上下游各因素的表达调控作用与NAFLD发病机制之间关系,就显得非常重要。本文总结了受SREBP2调控表达的靶基因的特点,着重介绍SREBP2调控胆固醇体内合成与平衡的信号通路与NAFLD发病机制之间关系,为研究和指导治疗NAFLD及其代谢性疾病提供新的思路。     

A Fad too Far? Dietary Strategies for the Prevention and Treatment of NAFLD

Nonalcoholic fatty liver disease (NAFLD) is a major health problem, and its prevalence has increased in recent years, concurrent with rising rates of obesity and other metabolic diseases. Currently, there are no FDA‐approved pharmacological therapies for NAFLD, and lifestyle interventions, including weight loss and exercise, remain the cornerstones for treatment. Manipulating diet composition and eating patterns may be a sustainable approach to NAFLD treatment. Dietary strategies including Paleolithic, ketogenic, Mediterranean, high‐protein, plant‐based, low‐carbohydrate, and intermittent fasting diets have become increasingly popular because of their purported benefits on metabolic disease. This review highlights what is currently known about these popular dietary approaches in the management of NAFLD in clinical populations with mechanistic insight from animal studies. It also identifies key knowledge gaps to better inform future preclinical and clinical studies aimed at the treatment of NAFLD.     

MicroRNAs in the Pathogenesis of Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD), or, more accurately, metabolic associated fatty liver disease, accounts for a large proportion of chronic liver disorders worldwide and is closely associated with other conditions such as cardiovascular disease, obesity, and type 2 diabetes mellitus. NAFLD ranges from simple steatosis to nonalcoholic steatohepatitis (NASH) and can progress to cirrhosis and, eventually, also hepatocellular carcinoma. The morbidity and mortality associated with NAFLD are increasing rapidly year on year. Consequently, there is an urgent need to understand the etiology and pathogenesis of NAFLD and identify effective therapeutic targets. MicroRNAs (miRNAs), important epigenetic factors, have recently been proposed to participate in NAFLD pathogenesis. Here, we review the roles of miRNAs in lipid metabolism, inflammation, apoptosis, fibrosis, hepatic stellate cell activation, insulin resistance, and oxidative stress, key factors that contribute to the occurrence and progression of NAFLD. Additionally, we summarize the role of miRNA-enriched extracellular vesicles in NAFLD. These miRNAs may comprise suitable therapeutic targets for the treatment of this condition.     

The expanding role of fish models in understanding non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is a condition in which excessive fat accumulates in the liver of an individual who has not consumed excessive alcohol. Non-alcoholic steatohepatitis (NASH), a severe form of NAFLD, can progress to hepatic cirrhosis and/or hepatocellular carcinoma (HCC). NAFLD is considered to be a hepatic manifestation of metabolic syndrome, and its incidence has risen worldwide in lockstep with the increased global prevalence of obesity. Over the last decade, rodent studies have yielded an impressive list of molecules associated with NAFLD and NASH pathogenesis. However, the identification of currently unknown metabolic factors using mammalian model organisms is inefficient and expensive compared with studies using fish models such as zebrafish (Danio rerio) and medaka (Oryzias latipes). Substantial advances in unraveling the molecular pathogenesis of NAFLD have recently been achieved through unbiased forward genetic screens using small fish models. Furthermore, these easily manipulated organisms have been used to great advantage to evaluate the therapeutic effectiveness of various chemical compounds for the treatment of NAFLD. In this Review, we summarize aspects of NAFLD (specifically focusing on NASH) pathogenesis that have been previously revealed by rodent models, and discuss how small fish are increasingly being used to uncover factors that contribute to normal hepatic lipid metabolism. We describe the various types of fish models in use for this purpose, including those generated by mutation, transgenesis, or dietary or chemical treatment, and contrast them with rodent models. The use of small fish in identifying novel potential therapeutic agents for the treatment of NAFLD and NASH is also addressed.     

胆汁酸受体在非酒精性脂肪性肝病中的作用

非酒精性脂肪性肝病(non-alcoholic fatty liver disease, NAFLD)作为一种慢性肝病,在全球的发病率逐年递增。胰岛素抵抗和脂质代谢紊乱,以及随后的炎症反应和纤维化的激活,在其发生发展过程中发挥重要作用。但是对其认识仍很欠缺,且临床尚缺乏有效的药物。科研人员正极力探索NAFLD的相关病因及治疗的新的突破口。胆汁酸是在肝中合成的众多代谢产物之一。除帮助脂肪消化吸收外,胆汁酸还作为信号分子激活胆汁酸受体,一种重要的转录调节因子而发挥效应,对维持机体正常生理代谢至关重要。越来越多的证据表明,胆汁酸受体的功能与NAFLD的发生发展关系密切,研究其相关的作用与功能可为治疗NAFLD提供新见解和药物治疗靶点。本文就胆汁酸受体包括核受体,诸如法尼醇X受体 (farnesoid X receptor, FXR)、孕烷X受体 (pregnane X receptor ,PXR)等,和细胞表面受体,诸如跨膜G蛋白偶联胆汁酸受体5(transmembrane G protein-coupled receptor 5, TGR5)、鞘氨醇-1-磷酸受体2(phingosine-1-phosphate receptor 2, S1PR2)和毒蕈碱胆碱受体3 (M3 muscarinic receptor, M3R)通过调节胆汁酸稳态、脂质和糖代谢、能量代谢、肝的炎症和纤维化等参与NAFLD发病机制的研究进展进行总结,并进一步阐述了胆汁酸受体激动剂对NAFLD的治疗现状,以期更全面地了解NAFLD的发病机制以及为治疗找到更有效的途径。     

Advancing the understanding of NAFLD to hepatocellular carcinoma development: From experimental models to humans

Nonalcoholic fatty liver disease (NAFLD) has recently been recognized as an important etiology contributing to the increased incidence of hepatocellular carcinoma (HCC). NAFLD, characterized by fat accumulation in the liver, is affecting at least one-third of the global population. The more aggressive form, nonalcoholic steatohepatitis (NASH), is characterized by hepatocyte necrosis and inflammation. The development of effective approaches for disease prevention and/or treatment heavily relies on deep understanding of the mechanisms underlying NAFLD to HCC development. However, this has been largely hampered by the lack of robust experimental models that recapitulate the full disease spectrum. This review will comprehensively describe the current in vitro and mouse models for studying NAFLD/NASH/HCC, and further emphasize their applications and possible future improvement for better understanding the molecular mechanisms involved in the cascade of NAFLD to HCC progression.     

Effect of Oleic Acid on the Levels of Eight Metal Ions in Human Hepatoma SMMC-7721 Cells

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. Its incidence is rising worldwide. However, no specific therapy has been shown to be effective in its treatment. In the present study, the in vitro NAFLD model was established in human SMMC-7721 cells by using oleic acid (OA). Then, content changes of eight cations, including sodium, magnesium, potassium, calcium, iron, copper, zinc, and manganese, were investigated in the experimental model. The results showed that OA induced a decrease in magnesium level, while an increase in iron one. Additionally, the supplementation of magnesium in the cell culture model was studied. It showed that magnesium ameliorated lipid accumulation induced by OA. Our results suggest that magnesium could decrease the risk of NAFLD and be used as a promising candidate for the treatment of NAFLD.     

非酒精性脂肪性肝病蛋白质组学研究进展

非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)是一种常见慢性肝脏疾病,其发病率呈逐年上升趋势,但发病机制尚未明确,诊疗手段仍不完善.蛋白质组学(proteomics)的出现使NAFLD研究有了进一步的发展,相关研究已达21个.目前,蛋白质组学技术可以研究疾病相关的分子改变,从而寻找新的生物标志物和治疗靶标.在此,对蛋白质组学在NAFLD诊断及分期、发病机制和其他相关领域研究进展作一个较为全面的综述.首先,对研究中遇到的研究对象、样本种类、实验方法和标志物特征选择进行经验性总结.其次,除了介绍如何运用蛋白质组学研究病因、危险因素和重要分子在NAFLD发病机制中的作用,还介绍NAFLD发病机制的亚细胞蛋白质组学、修饰蛋白质组学以及蛋白质组学与转录组学相结合的研究实例.此外,对差异蛋白质的分析策略和价值作了重点阐述,收集到一些有望成为NAFLD治疗靶标的候选分子.最后,结合新技术展望研究新空间,以期能够有助于推动蛋白质组学在寻找新的疾病标志物、探索疾病分子机制和治疗靶标中开辟新的途径.     

Roles of PPARs in NAFLD: potential therapeutic targets

Non-alcoholic fatty liver disease (NAFLD) is a liver pathology with increasing prevalence due to the obesity epidemic. Hence, NAFLD represents a rising threat to public health. Currently, no effective treatments are available to treat NAFLD and its complications such as cirrhosis and liver cancer. Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear receptors which regulate lipid and glucose metabolism as well as inflammation. Here we review recent findings on the pathophysiological role of PPARs in the different stages of NAFLD, from steatosis development to steatohepatitis and fibrosis, as well as the preclinical and clinical evidence for potential therapeutical use of PPAR agonists in the treatment of NAFLD. PPARs play a role in modulating hepatic triglyceride accumulation, a hallmark of the development of NAFLD. Moreover, PPARs may also influence the evolution of reversible steatosis toward irreversible, more advanced lesions. Presently, large controlled trials of long duration are needed to assess the long-term clinical benefits of PPAR agonists in humans. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease.