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非酒精性脂肪性肝病(non-alcoholic fatty liver disease,NAFLD)是一种胰岛素抵抗和遗传易感密切相关的代谢性应激肝损伤,其病理主要表现为肝实质细胞脂肪堆积。截至目前,NAFLD的发病机制尚未完全阐明,临床上仍缺少行之有效的治疗方法。因此,建立能够准确模拟NAFLD疾病发生、发展过程的动物模型是探索NAFLD病因及筛选治疗靶点的重要基础。本文对目前常见的NAFLD饮食、化学和基因动物模型进行总结并系统地比较各自优缺点,以期为选择合适的动物模型用于NAFLD研究提供参考。 相似文献
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非酒精性脂肪性肝病(nonalcoholic fatty liver disease, NAFLD)是一组除外酒精和其他明确肝损伤因素所致的代谢相关性疾病,包括单纯性脂肪肝(SFL)、脂肪性肝炎(NASH)及其相关性肝硬化。NAFLD 已经成为慢性肝病的主要致病因素,有统计显示发病率可高达20.09%[1]。虽然脂肪肝被认为是一个良性病变,但部分 NASH 可进展成肝硬化,甚至发生肝功能衰竭和肝癌,然而其机制尚不明确。良好的动物模型在研究 NAFLD 的发病机制中发挥重要作用。查阅国内外相关文献发现,NAFLD 动物模型以鼠科动物为主,可分为三类:营养诱发模型、药物中毒模型和基因模型。本文就目前各种鼠类模型的特点及其病理机制进行综述。 相似文献
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非酒精性脂肪性肝病动物模型研究进展 总被引:2,自引:0,他引:2
非酒精性脂肪性肝病(nonalcoholic fatty liverdisease, NAFLD)是包括单纯性脂肪肝、脂肪性肝炎、脂肪性肝纤维化及肝硬化的一组疾病, 与肥胖、糖尿病、胰岛素抵抗等代谢综合征的相关组分关系密切. NAFLD的发病机制目前尚未完全阐明, 治疗上也缺乏有效措施,建立高质量的动物模型有助于对疾病的深入研究. 本文综述了常用NAFLD动物模型的特点及研究进展. 相似文献
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维生素D不仅被定义为阳光维生素,目前也被认为是一种类固醇激素;不仅具有经典的调节钙磷代谢作用,亦具有抗炎、抗感染及免疫调节等功能。此文对非酒精性脂肪性肝病(NAFLD)患者的维生素D状态,维生素D在NAFLD进展中抗炎及抗纤维化作用机制,以及维生素D受体(VDR)基因多态性与NAFLD的关联等研究作一综述。 相似文献
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Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the Western world, and it persists at a high prevalence. NAFLD is characterised by the accumulation of triglycerides in the liver and includes a spectrum of histopathological findings, ranging from simple fatty liver through non-alcoholic steatohepatitis (NASH) to fibrosis and ultimately cirrhosis, which may progress to hepatocellular carcinoma. The pathogenesis of NAFLD is closely related to the metabolic syndrome and insulin resistance. Understanding the pathophysiology and treatment of NAFLD in humans has currently been limited by the lack of satisfactory animal models. The ideal animal model for NAFLD should reflect all aspects of the intricate etiopathogenesis of human NAFLD and the typical histological findings of its different stages. Within the past several years, great emphasis has been placed on the development of an appropriate model for human NASH. This paper reviews the widely used experimental models of NAFLD in rats. We discuss nutritional, genetic and combined models of NAFLD and their pros and cons. The choice of a suitable animal model for this disease while respecting its limitations may help to improve the understanding of its complex pathogenesis and to discover appropriate therapeutic strategies. Considering the legislative, ethical, economical and health factors of NAFLD, animal models are essential tools for the research of this disease. 相似文献
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Monjur Ahmed 《World journal of hepatology》2015,7(11):1450-1459
There is worldwide epidemic of non-alcoholic fatty liver disease(NAFLD). NAFLD is a clinical entity related to metabolic syndrome. Majority of the patients are obese but the disease can affect non-obese individuals as well. Metabolic factors and genetics play important roles in the pathogenesis of this disorder. The spectrum of disorders included in NAFLD are benign macrovesicular hepatic steatosis, non-alcoholic steatohepatitis, hepatic fibrosis, cirrhosis of liver and hepatocellular carcinoma. Although the disease remains asymptomatic most of the time, it can slowly progress to end stage liver disease. It will be the most common indication of liver transplantation in the future. It is diagnosed by abnormal liver chemistry, imaging studies and liver biopsy. As there are risks of potential complications during liver biopsy, many patients do not opt for liver biopsy. There are some noninvasive scoring systems to find out whether patients have advanced hepatic fibrosis. At the present time, there are limited treatment options which include lifestyle modification to loose weight, vitamin E and thioglitazones. Different therapeutic agents are being investigated for optimal management of this entity. There are some studies done on incretin based therapies in patients with NAFLD. Other potential agents will be silent information regulator protein Sirtuin and antifibrotic monoclonal antibody Simtuzumab against lysyl oxidase like molecule 2. But they are still in the investigational phase. 相似文献
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Nagarajan P Mahesh Kumar MJ Venkatesan R Majundar SS Juyal RC 《World journal of gastroenterology : WJG》2012,18(11):1141-1153
Nonalcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance, and type 2 diabetes. NAFLD represents a large spectrum of diseases ranging from (1) fatty liver (hepatic steatosis); (2) steatosis with inflammation and necrosis; to (3) cirrhosis. The animal models to study NAFLD/nonalcoholic steatohepatitis (NASH) are extremely useful, as there are still many events to be elucidated in the pathology of NASH. The study of the established animal models has provided many clues in the pathogenesis of steatosis and steatohepatitis, but these remain incompletely understood. The different mouse models can be classified in two large groups. The first one includes genetically modified (transgenic or knockout) mice that spontaneously develop liver disease, and the second one includes mice that acquire the disease after dietary or pharmacological manipulation. Although the molecular mechanism leading to the development of hepatic steatosis in the pathogenesis of NAFLD is complex, genetically modified animal models may be a key for the treatment of NAFLD. Ideal animal models for NASH should closely resemble the pathological characteristics observed in humans. To date, no single animal model has encompassed the full spectrum of human disease progression, but they can imitate particular characteristics of human disease. Therefore, it is important that the researchers choose the appropriate animal model. This review discusses various genetically modified animal models developed and used in research on NAFLD. 相似文献
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Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient without a history of alcohol abuse. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can progress to liver cirrhosis and hepatocellular carcinoma. NAFLD is regarded as a hepatic manifestation of metabolic syndrome and incidence has been increasing worldwide in line with the increased prevalence of obesity, type 2 diabetes, and hyperlipemia. Animal models of NAFLD/NASH give crucial information, not only in elucidating pathogenesis of NAFLD/NASH but also in examining therapeutic effects of various agents. An ideal model of NAFLD/NASH should correctly reflect both hepatic histopathology and pathophysiology of human NAFLD/NASH. Animal models of NAFLD/NASH are divided into genetic, dietary, and combination models. In this paper, we review commonly used animal models of NAFLD/NASH referring to their advantages and disadvantages. 相似文献
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Maria Martin-Grau Vannina G Marrachelli Daniel Monleon 《World journal of hepatology》2022,14(2):304-318
Non-alcoholic fatty liver disease (NAFLD) prevalence has increased drastically in recent decades, affecting up to 25% of the world’s population. NAFLD is a spectrum of different diseases that starts with asymptomatic steatosis and continues with development of an inflammatory response called steatohepatitis, which can progress to fibrosis. Several molecular and metabolic changes are required for the hepatocyte to finally vary its function; hence a “multiple hit” hypothesis seems a more accurate proposal. Previous studies and current knowledge suggest that in most cases, NAFLD initiates and progresses through most of nine hallmarks of the disease, although the triggers and mechanisms for these can vary widely. The use of animal models remains crucial for under standing the disease and for developing tools based on biological knowledge. Among certain requirements to be met, a good model must imitate certain aspects of the human NAFLD disorder, be reliable and reproducible, have low mortality, and be compatible with a simple and feasible method. Metabolism studies in these models provides a direct reflection of the workings of the cell and may be a useful approach to better understand the initiation and progression of the disease. Metabolomics seems a valid tool for studying metabolic pathways and crosstalk between organs affected in animal models of NAFLD and for the discovery and validation of relevant biomarkers with biological understanding. In this review, we provide a brief introduction to NAFLD hallmarks, the five groups of animal models available for studying NAFLD and the potential role of metabolomics in the study of experimental NAFLD. 相似文献
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Amedeo Lonardo Stefano Ballestri Alessandro Mantovani Fabio Nascimbeni Simonetta Lugari Giovanni Targher 《Digestive and liver disease》2019,51(4):462-470
Nonalcoholic fatty liver disease (NAFLD), the most common liver disease worldwide, may be associated with primary hypothyroidism. However, the pathogenesis underlying such an association is complex and not completely understood. Here, we specifically discuss the pathogenic mechanisms potentially involved in hypothyroidism-induced NAFLD. To this end, we summarize the general pathophysiology of thyroid hormones (TH). Next, we analyze the published data from rodent studies by discussing whether hypothyroid rats may develop NAFLD via hyperphagia; whether mitochondria become energetically more efficient; what the overall energy balance is and if diversion of fatty substrates occurs; and the latest advancements in molecular pathogenesis brought about by metabolomics, cell imaging, lipophagy, autophagy and genetically engineered mouse models. Moreover, we discuss the data published regarding humans on the pathogenic role of TH, metabolic syndrome and other risk factors in hypothyroidism-related NAFLD as well as the putative mechanisms underlying the development of NAFLD-related hepatocellular carcinoma in hypothyroidism. In conclusion, although many research questions still remain unanswered, the pathophysiology of hypothyroidism-induced NAFLD makes this a potentially curable and distinct disease entity. However, further studies are needed to better elucidate the underlying mechanisms, and to ascertain whether treatment with either TH or thyromimetic agents improves NAFLD. 相似文献
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Braunersreuther V Viviani GL Mach F Montecucco F 《World journal of gastroenterology : WJG》2012,18(8):727-735
Non-alcoholic fatty liver disease (NAFLD) includes a variety of histological conditions (ranging from liver steatosis and steatohepatitis, to fibrosis and hepatocarcinoma) that are characterized by an increased fat content within the liver. The accumulation/deposition of fat within the liver is essential for diagnosis of NAFLD and might be associated with alterations in the hepatic and systemic inflammatory state. Although it is still unclear if each histological entity represents a different disease or rather steps of the same disease, inflammatory processes in NAFLD might influence its pathophysiology and prognosis. In particular, non-alcoholic steatohepatitis (the most inflamed condition in NAFLDs, which more frequently evolves towards chronic and serious liver diseases) is characterized by a marked activation of inflammatory cells and the upregulation of several soluble inflammatory mediators. Among several mediators, cytokines and chemokines might play a pivotal active role in NAFLD and are considered as potential therapeutic targets. In this review, we will update evidence from both basic research and clinical studies on the potential role of cytokines and chemokines in the pathophysiology of NAFLD. 相似文献
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Non-alcoholic fatty liver disease (NAFLD) has become an increasingly epidemic metabolic disease worldwide. NAFLD can gradually deteriorate from simple liver steatosis, inflammation and fibrosis to liver cirrhosis and/or hepatocellular carcinoma. Zebrafish are vertebrate animal models that are genetically and metabolically conserved with mammals and have unique advantages such as high fecundity, rapid development ex utero and optical transparency. These features have rendered zebrafish an emerging model system for liver diseases and metabolic diseases favoured by many researchers in recent years. In the present review, we summarize a series of tools for zebrafish NAFLD research and the models established through different dietary feeding, hepatotoxic chemical treatments and genetic manipulations via transgenic or genome editing technologies. We also discuss how zebrafish models facilitate NAFLD studies by providing novel insights into NAFLD pathogenesis, toxicology research, and drug evaluation and discovery. 相似文献
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Charlotte J. Green PhD Thomas Marjot MBBCH Jeremy W. Tomlinson FRCP Leanne Hodson PhD 《Diabetes, obesity & metabolism》2019,21(4):749-760
Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver diseases, of which the first stage is steatosis. It is one of the most common liver diseases in developed countries and there is a clear association between type 2 diabetes (T2DM) and NAFLD. It is estimated that 70% of people with T2DM have NAFLD and yet there is currently no licensed pharmacological agent to treat it. Whilst lifestyle modification may ameliorate liver fat, it is often difficult to achieve or sustain; thus, there is great interest in pharmacological treatments for NAFLD. Metformin is the first-line medication in the management of T2DM and evidence from animal and human studies has suggested that it may be useful in reducing liver fat via inhibition of lipogenesis and increased fatty acid oxidation. Findings from the majority of studies undertaken in rodent models clearly suggest that metformin may be a powerful therapeutic agent specifically to reduce liver fat accumulation; data from human studies are less convincing. In the present review we discuss the evidence for the specific effects of metformin treatment on liver fat accumulation in animal and human studies, as well as the underlying proposed mechanisms, to try and understand and reconcile the difference in findings between rodent and human work in this area. 相似文献
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Tannaz Eslamparast Sareh Eghtesad Hossein Poustchi Azita Hekmatdoost 《World journal of hepatology》2015,7(2):204-212
Nonalcoholic fatty liver disease(NAFLD) is currently known as the most common liver problem, characterized by excessive lipid accumulation in hepatocytes,which may progress to other liver diseases such as nonalcoholic steatohepatitis, hepatic tissue fibrosis, livercirrhosis, and failure or hepatocellular carcinoma. Since NAFLD is positively associated with the development of obesity, insulin resistance, and ultimately type 2 diabetes mellitus, it is often regarded as the hepatic manifestation of the metabolic syndrome. No pharmacologic treatment has yet been proven for this disease. For most patients with presumed or confirmed NAFLD, the only proven strategy is to offer lifestyle advice that can lead to sustained weight loss. Since insulin resistance, oxidative stress, inflammation, and necro-apoptosis are involved in NAFLD pathogenesis, it seems that every potential therapeutic agent should target one or some of these pathologic events. There are many well known anti-oxidants, anti-inflammatory, and insulin sensitizer dietary supplements which have shown beneficial effects on NAFLD improvement in animal and human studies. The purpose of this review is to explore the existing evidences on dietary supplements considered to have hepatoprotective properties, and to present some proposed mechanisms by which they may protect against NAFLD. 相似文献