运动诱导细胞自噬在非酒精性脂肪性肝病防治中的作用

非酒精性脂肪性肝病(NAFLD)是一种以慢性肝损伤为主要特征的代谢性疾病。流行病学调查显示,NAFLD的发病率呈现不断上升的趋势，已严重威胁人类的生命健康。研究表明，自噬失调是NAFLD的重要病理生理机制，运动作为一种重要的非药物治疗手段，可通过诱导细胞自噬起到防治NAFLD的作用，但其确切机制尚不清楚。本文梳理与总结自噬与NAFLD的关系、运动诱导细胞自噬对NAFLD的影响以及其潜在分子机制的相关理论研究和应用成果，以期为NAFLD的预防与治疗提供理论参考。     

自噬与氧化应激在非酒精性脂肪性肝病发病机制中的关系

非酒精性脂肪性肝病(NAFLD)是多种因素共同作用的结果,而以氧化应激为中心的"第二次打击"是NAFLD进展的关键因素。自噬作为近年来的研究热点,越来越多的证据显示自噬在肝细胞脂质代谢、炎症反应与肝纤维化中发挥重要作用,且与氧化应激有着密切关系。结合当前国内外最新研究成果分别从自噬与NAFLD的关系、氧化应激与NAFLD的关系分析自噬与氧化应激在NAFLD发病机制中的相互关系,指出自噬在NAFLD发病进程中调控氧化应激的分子机制可能成为今后的研究热点,若能够阻断或者激活自噬调控氧化应激的某个关键通路,或可为干预NAFLD提供新的手段。     

郭朋主任医师治疗非酒精性脂肪性肝病的经验

非酒精性脂肪性肝病(NAFLD)是一种与胰岛素抵抗(IR)和遗传易感密切相关的代谢应激性肝损伤,疾病谱包括非酒精性肝脂肪变、非酒精性脂肪性肝炎(NASH)、肝硬化和肝细胞癌。NAFLD不仅可以导致肝病残疾和死亡,还与代谢综合征(MetS)、2型糖尿病(T2DM)、动脉硬化性心血管疾病以及结直肠肿瘤等疾病高发密切相关。随着肥胖和MetS的流行,NAFLD已成为我国第一大慢性肝病和健康体检肝脏生物化学指标异常的首要原因[1]。     

多囊卵巢综合征与非酒精性脂肪性肝病

非酒精性脂肪性肝病(non-alcoholic fatty liverdisease,NAFLD)是一种与胰岛素抵抗和遗传易感密切相关的获得性代谢应激性肝损伤,疾病谱包括单纯性脂肪肝、非酒精性脂肪性肝炎(non-alcoholicsteatohepatitis,NASH)及其相关肝硬化.NAFLD的肝组织学改变与酒精性肝病相似,但无过量饮酒史和其他明确损肝因素存在.随着生活方式的改变,NAFLD已成为西方发达国家和我国富裕地区慢性肝病的首要病因 [1],导致失代偿期肝硬化、2型糖尿病、动脉粥样硬化以及代谢综合征相关恶性肿瘤的发生率升高.     

哺乳动物雷帕霉素靶蛋白C1(mTORC1)在非酒精性脂肪性肝病治疗中的作用机制及潜力

非酒精性脂肪性肝病(NAFLD)已成为全球最常见的慢性肝病，可进展为非酒精性脂肪性肝炎、肝硬化和肝癌。哺乳动物雷帕霉素靶蛋白(mTOR)是一种非典型丝氨酸/苏氨酸蛋白激酶，在细胞生长、凋亡、自噬及代谢等过程中发挥了极为重要的作用。本文阐述mTORC1信号通路在NAFLD发病过程中对细胞代谢和生长分化的作用，进一步提出mTORC1通路对于NAFLD治疗药物的研究价值和潜力。     

脂肪性肝炎对于非酒精性脂肪性肝病预后判断仍很重要

正非酒精性脂肪性肝病(NAFLD)是一种与遗传易感和胰岛素抵抗密切相关的慢性代谢应激性肝病,疾病谱包括单纯性脂肪肝、非酒精性脂肪性肝炎(NASH)及其相关肝硬化[1-4]。随着肥胖、糖尿病和代谢综合征的流行,NAFLD已成为全球第一大慢性肝脏疾病,与失代偿期肝硬化、肝功能衰竭、肝细胞癌的高发密切相关[1-4]。尽管此前医学界花了10余年时间才认识到丙型肝炎病毒(HCV)感染是终末期肝病的重要原因,现在我们同样经历了漫长时间才逐渐意识到NASH的巨大危害,     

肝内微环境诱导的自噬在非酒精性脂肪性肝病中的作用

非酒精性脂肪性肝病(NAFLD)是以肝细胞内脂质过度沉积为主要特征的一系列肝脏异常病变，也是全球范围内最常见的慢性肝病。自噬是细胞降解自身成分、参与维持器官功能及机体稳态的一种基本细胞过程，与NAFLD的进展存在密切联系。机体遭受的高脂、缺氧和压力等在肝脏内形成了细胞外微环境的异常改变，这些异常微环境可能通过诱导的肝脏细胞自噬促进NAFLD的发生发展。本文基于肝脏内的多种微环境特征，对肝细胞、Kupffer细胞、肝星状细胞等肝脏细胞的自噬在NAFLD进展中的作用和机制进行综述。     

非酒精性脂肪性肝病药物研发终点必须为临床获益

<正>非酒精性脂肪性肝病(nonalcoholic fatty liver disease,NAFLD)的疾病谱包括非酒精性单纯性脂肪肝(nonalcoholic fatty liver,NAFL)、非酒精性脂肪性肝炎(nonalcoholic steatohepatitis,NASH)及其相关肝硬化。随着肥胖症、糖尿病和代谢综合征全球化流行趋势,NAFLD现已成为包括我国在内的世界诸多国家和地区慢性肝脏疾病的首要病因。NAFLD不仅增加肝脏疾病残疾和死亡而且增加心血管事件相关死亡     

自噬与非酒精性脂肪性肝病调控相关因子的关系

非酒精性脂肪性肝病(NAFLD)是一种常见疾病,病理表现为肝细胞内脂肪滴大量蓄积。NAFLD不仅成因复杂,还可诱发心血管疾病、糖尿病等,然而目前尚无有效的治疗手段和专门的治疗药物。自噬在真核生物中普遍存在,具有维持细胞内稳态的作用。自噬选择性降解细胞中脂质的机制称为脂噬,该机制为缓解因脂质蓄积引起的疾病提供了新思路。从NAFLD发生发展、脂肪滴降解过程、肝脏炎症和纤维化进展相关因子入手,探讨了自噬与NAFLD的相关性。这可能为从自噬入手治疗NAFLD提供理论基础,并为相关药物的研发提供作用靶点。     

Betatrophin与非酒精性脂肪性肝病

目的 非酒精性脂肪性肝病(NAFLD)是一种代谢应激性肝损伤。随着肥胖和代谢综合征(MetS)的流行,NAFLD已成为我国第一大慢性肝病。Betatrophin是一种新发现的与糖脂代谢和胰岛素抵抗(IR)等密切相关的分泌性糖蛋白,可能与NAFLD患者发病和病情进展密切相关。本文就Betatrophin在NAFLD发生发展过程中的作用和潜在的临床应用价值做一综述。     

胰高血糖素样肽-1改善非酒精性脂肪性肝病作用机制研究进展*

近期研究表明,胰高血糖素样肽-1受体激动剂可从改善肝细胞脂质代谢、抑制炎症反应、调节细胞自噬等多个环节减轻非酒精性脂肪性肝病（NAFLD）患者肝脏脂质沉积,改善组织学损伤,有望成为治疗NAFLD药物的新选择。     

Non-alcoholic fatty liver disease and type 2 diabetes mellitus: The liver disease of our age?

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that might affect up to one-third of the adult population in industrialised countries. NAFLD incorporates histologically and clinically different non-alcoholic entities; fatty liver (NAFL, steatosis hepatis) and steatohepatitis (NASH-characterised by hepatocyte ballooning and lobular inflammation ± fibrosis) might progress to cirrhosis and rarely to hepatocellular cancer. NAFL increasingly affects children (paediatric prevalence is 4.2%-9.6%). Type 2 diabetes mellitus (T2DM), insulin resistance (IR), obesity, metabolic syndrome and NAFLD are particularly closely related. Increased hepatic lipid storage is an early abnormality in insulin resistant women with a history of gestational diabetes mellitus. The accumulation of triacylglycerols in hepatocytes is predominantly derived from the plasma nonesterified fatty acid pool supplied largely by the adipose tissue. A few NAFLD susceptibility gene variants are associated with progressive liver disease, IR, T2DM and a higher risk for hepatocellular carcinoma. Although not approved, pharmacological approaches might be considered in NASH patients.     

The interaction of hepatic lipid and glucose metabolism in liver diseases

It is widely known that the liver is a central organ in lipogenesis, gluconeogenesis and cholesterol metabolism. However, over the last decades, a variety of pathological conditions highlighted the importance of metabolic functions within the diseased liver. As observed in Western societies, an increase in the prevalence of obesity and the metabolic syndrome promotes pathophysiological changes that cause non-alcoholic fatty liver disease (NAFLD). NAFLD increases the susceptibility of the liver to acute liver injury and may lead to cirrhosis and hepatocellular cancer. Alterations in insulin response, β-oxidation, lipid storage and transport, autophagy and an imbalance in chemokines and nuclear receptor signaling are held accountable for these changes. Furthermore, recent studies revealed a role for lipid accumulation in inflammation and ER stress in the clinical context of liver regeneration and hepatic carcinogenesis. This review focuses on novel findings related to nuclear receptor signaling - including the vitamin D receptor and the liver receptor homolog 1 - in hepatic lipid and glucose uptake, storage and metabolism in the clinical context of NAFLD, liver regeneration, and cancer.     

Insulin resistance and metabolic syndrome in chronic liver diseases: old entities with new implications

Insulin resistance (IR) and metabolic syndrome have recently been implicated in the pathogenesis and progression of chronic liver diseases, especially chronic hepatitis C (CHC) and non-alcoholic fatty liver disease (NAFLD). In this review, we provide current information on their deleterious effect on the liver, with particular interest in those two entities. In NAFLD, IR causes both the accumulation of fat in hepatocytes and the progression to non-alcoholic steatohepatitis (NASH). Moreover, the presence of metabolic syndrome seems to be associated with severe fibrosis in NASH patients. In CHC, IR develops early in the course of the disease and precedes steatosis. It is also independently associated with histological severity and negatively affects treatment response, irrespective of genotype. Consequently, therapies targeting IR and metabolic syndrome could indirectly ameliorate the prognosis of both NAFLD and CHC. As specific therapies do not exist, patients with metabolic syndrome and CHC and NAFLD should be counseled to lose weight and ameliorate their glycemic control and lipid profile.     

磁共振技术对脂肪性肝病诊断的进展

随着人群中肥胖及糖尿病发病率的升高,非酒精性脂肪性肝病(NAFLD)在众多国家成为最常见的慢性肝病.疾病谱随病程的进展表现不一,包括单纯脂肪肝、脂肪性肝炎、脂肪性肝纤维化和肝硬化.虽然单纯性脂肪肝的预后良好,但是脂肪性肝炎仍可进一步发展成肝硬化、肝癌,甚至发生肝衰竭而导致死亡,所以对脂肪肝及相关肝病的诊断越发受到人们重视.目前肝脏活检是诊断脂肪肝的金标准,但是由于活检自身的限制需要发展有效的非侵入性检查方法.其中,磁共振技术作为一项非侵入性检查手段,在对脂肪性肝病的早期诊断方面具有广阔的应用前景.本文主要从三方面列举并评估了磁共振技术对脂肪性肝病的诊断进展.     

改善胰岛素抵抗治疗NAFLD/NASH的循证证据

非酒精性脂肪性肝病/非酒精性脂肪性肝炎(NAFLD/NASH)是指除外酒精和其他明确的肝损伤因素所致的以肝细胞脂肪沉积为特征的临床病理综合征。胰岛素抵抗(IR)与NAFLD/NASH的发病密切相关,因此改善IR或许可以减轻肝损伤。多项随机对照临床试验显示胰岛素增敏剂和逐渐减轻体质量(饮食疗法或体育锻炼等)对NAFLD的治疗有一定作用,但长期疗效尚不明确。本文对近年关于改善IR治疗NAFLD/NASH的临床试验作一综述。     

中老年人血尿酸水平与非酒精性脂肪性肝病的相关性研究

目的:研究中老年人群血尿酸水平与非酒精性脂肪性肝病(NAFLD)的相关性。方法 :采取整群抽样方法,对上海市嘉定社区2 519名40岁以上常住居民进行问卷调查、体格检查,同时采血进行血尿酸、血糖、血脂、肝功能、肾功能检测,以及上腹部彩色多普勒超声检查。NAFLD的诊断依据高分辨率超声扫描结果。按照血尿酸水平四分位数将研究人群分为Q1、Q2、Q3、Q4四组,并对其各项代谢指标进行分析。结果:NAFLD组的血尿酸水平显著高于非NAFLD组[(319.6±92.3)比(272.8±88.8)μmol/L,P<0.05)。结论:上海城镇中老年人群NAFLD患病风险随着血尿酸水平升高而增加。     

成人非酒精性脂肪肝与代谢综合征相关性分析

目的分析成人非酒精性脂肪肝病（NAFLD）和代谢综合征（MS）的关系。方法对2007年6月～10月广元市北街社区3180例20岁以上居民进行体格检查及肝脏B超检查,并检测空腹血糖（FBG）、血脂和丙氨酸氨基转氨酶（ALT）。结果（1）NAFLD患病率为13．5％,MS患病率为16．5％,丽病共患率为9．5％。（2）MS、中心性肥胖、血压升高、FBG升高、高甘油三酯（TG）、高密度脂蛋白（HLD—C）降低,各组NAFLD患病风险是对照组的12．7～24．1倍。（3）以NAFLD取代诊断MS的5个组分中的任何一个后,与原诊断定义相比有较高的一致性。结论该社区中1／8以上人群患有NAFLD或MS,且NAFLD与MS密切相关,NAFLD可能是MS的重要组成成分。     

非酒精性脂肪性肝病相关慢性肾病研究进展

非酒精性脂肪性肝病是与胰岛素抵抗和遗传易感性密切相关的代谢应激性肝损伤。该病已经成为全球性的公共卫生问题之一。近几年来,有研究显示非酒精性脂肪性肝病可能与慢性肾病越来越高的患病率有关。本文将重点阐述这两个疾病的相互关系以及相关发生机制,比如胰岛素抵抗、炎症、氧化应激、高凝状态、胎球蛋白-A和脂联素等在该病发病中的作用,为更全面管理非酒精性脂肪性肝病患者和慢性肾病患者提供有用的建议。     

Non-alcoholic fatty liver disease and psoriasis: So far,so near

Psoriasis is a chronic inflammatory immune-mediated skin diseases which is frequently associated to comorbidities. Non-alcoholic fatty liver disease(NAFLD) is defined as an excessive accumulation of triglycerides in hepatocytes and includes a wide spectrum of liver conditions ranging from relatively benign steatosis to non-alcoholic steatohepatitis with fatty infiltration and lobular inflammation and to cirrhosis and endstage liver disease. Actually, psoriasis is considered a systemic diseases associated to comorbidities, as metabolic syndrome and NAFLD is seen the hepatic manifestation of the metabolic syndrome. The possible link between psoriasis, obesity and metabolic syndrome, which are known risk factors for NAFLD has beenrecently documented focusing in the crucial role of the adipose tissue in the development of the inflammatory background sharing by the above entities. According to recent data, patients with psoriasis show a greater prevalence of NAFLD and metabolic syndrome than the general population. Moreover, patients with NAFLD and psoriasis are at higher risk of severe liver fibrosis than those with NAFLD and without psoriasis. The link between these pathological conditions appears to be a chronic low-grade inflammatory status. The aim of this review is to focus on the multiple aspects linking NAFLD and psoriasis, only apparently far diseases.