非酒精性脂肪性肝病动物模型研究进展*

doi:10.3969/j.issn.1672-5069.2021.05.039

实用肝脏病杂志 ›› 2021, Vol. 24 ›› Issue (5): 761-764.doi: 10.3969/j.issn.1672-5069.2021.05.039

• 综述 • 上一篇

非酒精性脂肪性肝病动物模型研究进展^*

张译之, 张晓慧综述, 陈煜审校

100069 北京市首都医科大学附属北京佑安医院疑难肝病及人工肝中心/肝衰竭与人工肝治疗研究北京市重点实验室

收稿日期:2020-03-30 发布日期:2021-10-21
通讯作者: 张晓慧,女,40岁,研究员。主要从事肝衰竭、脂肪肝和肝纤维化防治研究。E-mail: zhangxiaohui_111@163.com
作者简介:张译之,女,28岁,博士研究生。主要从事肝衰竭和脂肪肝防治研究。E-mail:1026263506@qq.com
基金资助:
^* 国家自然科学基金资助项目(编号:81500472);国家重点研发计划资助项目(编号:2017YFA0103000);国家科技重大专项“艾滋病和病毒性肝炎等重大传染病防治”专项基金资助项目(编号:2017ZX10203201-005/2017ZX10201201-001-001/2017ZX10201201-002-002/2017ZX10201201-004-002/2017ZX10202203-006-001/2017ZX10302201-004-002);北京市自然科学基金资助项目(编号:7202070);天晴肝病研究基金资助项目(编号:TQGB20200101);北京市医院管理局临床医学发展专项经费资助项目(编号:ZYLX201806)

Models of nonalcoholic fatty liver disease

Zhang Yizhi, Zhang Xiaohui, Chen Yu

Municipal Key Laboratory of Liver Failure and Artificial Liver Treatment Research, Artificial Liver Center, You’an Hospital, Capital Medical University, Beijing 100069, China

Received:2020-03-30 Published:2021-10-21

摘要/Abstract

摘要： 目的非酒精性脂肪性肝病(NAFLD)发病率逐年增加,并可能发展成为终末期肝病。目前,仍缺乏针对该病的治疗药物,建立动物模型研究很有必要。尽管已有多种不同种类的疾病模型,但仍没有一种能真正反映人类整个疾病谱的代表性的NAFLD模型。本文对目前应用的NAFLD模型进行了综述,重点介绍动物模型、2D细胞模型和3D肝脏模型及其优缺点。

关键词: 非酒精性脂肪性肝病, 细胞模型, 动物模型, 组织工程肝脏

Abstract: Objective The incidence rate of nonalcoholic fatty liver disease (NAFLD) is increasing. It might progress to the end-stage liver disease. However, there is still no specific treatment for this entity. Therefore, the establishment of representative animal models reflecting disease characteristics has become especially important. Although there are many different disease models, there is still a lack of NAFLD model which could cover the whole spectrum of this entity in human. In this paper, we reviewed the current progress on NAFLD model, focusing on animal model, 2D cell model, 3D liver model and their advantages and disadvantages.

Key words: Nonalcoholic fatty liver disease, Cell model, Animal model, Tissue engineering liver

张译之, 张晓慧, 陈煜. 非酒精性脂肪性肝病动物模型研究进展^*[J]. 实用肝脏病杂志, 2021, 24(5): 761-764.

Zhang Yizhi, Zhang Xiaohui, Chen Yu. Models of nonalcoholic fatty liver disease[J]. Journal of Practical Hepatology, 2021, 24(5): 761-764.

参考文献

[1]Marchisello S, Di Pino A, Scicali R, et al. Pathophysiological, molecular and therapeutic issues of nonalcoholic fatty liver disease: An overview. Int J Mol Sci, 2019, 20(8): 1948.
[2]Friedman S L, Neuschwander-Tetri B A, Rinella M, et al. Mechanisms of NAFLD development and therapeutic strategies. Nature Medicine, 2018, 24(7): 908-922.
[3]Solinas P, Isola M, Lilliu M A, et al. Animal models are reliably mimicking human diseases? A morphological study that compares animal with human NAFLD. Microsc Res Tech, 2014, 77(10): 790-796.
[4]Trak-Smayra V, Paradis V, Massart J, et al. Pathology of the liver in obese and diabetic ob/ob and db/db mice fed a standard or high-calorie diet. Int J Exp Pathol, 2011, 92(6): 413-421.
[5]Yang S Q, Lin H Z, Lane M D, et al. Obesity increases sensitivity to endotoxin liver injury: Implications for the pathogenesis of steatohepatitis. Proc Natl Acad Sci U S A, 1997, 94(6): 2557-2562.
[6]Leclercq I A, Farrell G C, Schriemer R, et al. Leptin is essential for the hepatic fibrogenic response to chronic liver injury. J Hepatol, 2002, 37(2): 206-213.
[7]Gupta A, Leslie N R. Controlling PTEN (phosphatase and tensin homolog) stability: A dominant role for lysine 66. J Biol Chem, 2016, 291(35): 18465-18473.
[8]Zhang X. NAFLDrelated-HCC: The relationship with metabolic disorders. Adv Exp Med Biol, 2018, 1061: 55-62.
[9]Stiles B, Wang Y, Stahl A, et al. Liver-specific deletion of negative regulator Pten results in fatty liver and insulin hypersensitivity [corrected]. Proc Natl Acad Sci U S A, 2004, 101(7): 2082-2087.
[10] Horie Y, Suzuki A, Kataoka E, et al. Hepatocyte-specific Pten deficiency results in steatohepatitis and hepatocellular carcinomas. J Clin Invest, 2004, 113(12): 1774-1783.
[11] Nakayama H, Otabe S, Ueno T, et al. Transgenic mice expressing nuclear sterol regulatory element-binding protein 1c in adipose tissue exhibit liver histology similar to nonalcoholic steatohepatitis. Metabolism, 2007, 56(4): 470-475.
[12] Eccleston H B, Andringa K K, Betancourt A M, et al. Chronic exposure to a high-fat diet induces hepatic steatosis, impairs nitric oxide bioavailability, and modifies the mitochondrial proteome in mice. Antioxid Redox Signal, 2011, 15(2): 447-459.
[13] Asgharpour A, Cazanave S C, Pacana T, et al. A diet-induced animal model of non-alcoholic fatty liver disease and hepatocellular cancer. J Hepatol, 2016, 65(3): 579-588.
[14] Subramanian S, Goodspeed L, Wang S, et al. Dietary cholesterol exacerbates hepatic steatosis and inflammation in obese LDL receptor-deficient mice. J Lipid Res, 2011, 52(9): 1626-1635.
[15] Savard C, Tartaglione E V, Kuver R, et al. Synergistic interaction of dietary cholesterol and dietary fat in inducing experimental steatohepatitis. Hepatology, 2013, 57(1): 81-92.
[16] Takahashi Y, Soejima Y, Fukusato T. Animal models of nonalcoholic fatty liver disease /nonalcoholic steatohepatitis. World J Gastroenterol, 2012, 18(19): 2300-2308.
[17] Matsuzawa N, Takamura T, Kurita S, et al. Lipid-induced oxidative stress causes steatohepatitis in mice fed an atherogenic diet. Hepatology, 2007, 46(5): 1392-1403.
[18] Subramanian S, Goodspeed L, Wang S, et al. Dietary cholesterol exacerbates hepatic steatosis and inflammation in obese LDL receptor-deficient mice. J Lipid Res, 2011, 52(9): 1626-1635.
[19] Kohli R, Kirby M, Xanthakos S A, et al. High-fructose, medium chain trans fat diet induces liver fibrosis and elevates plasma coenzyme Q9 in a novel murine model of obesity and nonalcoholic steatohepatitis. Hepatology, 2010, 52(3): 934-944.
[20] Zhang X, Han J, Man K, et al. CXC chemokine receptor 3 promotes steatohepatitis in mice through mediating inflammatory cytokines, macrophages and autophagy. J Hepatol, 2016, 64(1): 160-170.
[21] Kirsch R, Clarkson V, Shephard E G, et al. Rodent nutritional model of non‐alcoholic steatohepatitis: Species, strain and sex difference studies. J Gastroenterol Hepatol, 2003, 18(11): 1272-1282.
[22] De Minicis S, Agostinelli L, Rychlicki C, et al. HCC development is associated to peripheral insulin resistance in a mouse model of NASH. PLoS One, 2014, 9(5): e97136.
[23] 张玉佩, 孔怡琳, 杨钦河, 等. Nrf2/ARE通路相关因子在脂肪变性HepG2细胞中的表达及其意义. 中国应用生理学杂志, 2016, 32(1): 13-17.
[24] Ozyra M, Johansson I, Nordling A, et al. Human hepatic 3D spheroids as a model for steatosis and insulin resistance. Sci Rep, 2018, 8(1): 14297.
[25] 张程亮, 贺雯茜, 徐艳娇, 等. 果糖诱导非酒精性脂肪性肝病小鼠动物模型的构建和评价. 肝脏, 2017, 22(8): 700-704.
[26] 贺雯茜, 杨金玉, 徐艳娇, 等. 果糖诱导肝脂肪变性细胞模型建立及评价. 肝脏, 2019, 24(6): 638-642.
[27] Wang Y, Nicolas C T, Chen H S, et al. Recent advances in decellularization and recellularization for tissue-engineered liver grafts. Cells Tissues Organs, 2017, 203(4): 203-214.
[28] Yamada M, Utoh R, Ohashi K, et al. Controlled formation of heterotypic hepatic micro-organoids in anisotropic hydrogel microfibers for long-term preservation of liver-specific functions. Biomaterials, 2012, 33(33): 8304-8315.
[29] Rennert K, Steinborn S, Groger M, et al. A microfluidically perfused three dimensional human liver model. Biomaterials, 2015, 71: 119-131.
[30] Li Q, Uygun B E, Geerts S, et al. Proteomic analysis of naturally-sourced biological scaffolds. Biomaterials, 2016, 75: 37-46.
[31] Uygun B E, Soto-Gutierrez A, Yagi H, et al. Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix. Nat Med, 2010, 16(7): 814-820.
[32] Wu Q, Liu J, Liu L, et al. Establishment of an ex vivo model of nonalcoholic fatty liver disease using a tissue-engineered liver. ACS Biomater Sci Engin, 2018, 4(8): 3016-3026.
[33] Fakhoury-Sayegh N, Trak-Smayra V, Khazzaka A, et al. Characteristics of nonalcoholic fatty liver disease induced in wistar rats following four different diets. Nutr Res Pract, 2015, 9(4): 350-357.
[34] Perfield J W, Ortinau L C, Pickering R T, et al. Altered hepatic lipid metabolism contributes to nonalcoholic fatty liver disease inleptin-deficient Ob/Ob mice. J Obes, 2013, 2013: 1-8.
[35] Schattenberg J M, Galle P R. Animal models of non-alcoholic steatohepatitis: Of mice and man. Dig Dis, 2010, 28(1): 247-254.

非酒精性脂肪性肝病动物模型研究进展^*

Models of nonalcoholic fatty liver disease

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