非酒精性脂肪性肝病体外模型的研究进展

卢晓臣; 韩红梅

doi:10.3969/j.issn.1001-5256.2022.01.035

非酒精性脂肪性肝病体外模型的研究进展

DOI: 10.3969/j.issn.1001-5256.2022.01.035

卢晓臣,
韩红梅^,

延边大学附属医院消化内科，吉林延吉 133000

基金项目:

国家自然科学基金 (81860110)

利益冲突声明：所有作者均声明不存在利益冲突。

作者贡献声明：卢晓臣负责分析资料，撰写论文，修改论文；韩红梅负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
韩红梅，hanhm79@126.com

计量
- 文章访问数: 1095
- HTML全文浏览量: 460
- PDF下载量: 202
- 被引次数: 0
出版历程
- 收稿日期: 2021-05-19
- 录用日期: 2021-06-03
- 出版日期: 2022-01-20

Research advances in in vitro models for nonalcoholic fatty liver disease

Xiaochen LU,
Hongmei HAN^,

Department of Gastroenterology, The Affiliated Hospital of Yanbian University, Yanji, Jilin 133000, China

Research funding:

National Natural Science Foundation of China (81860110)

摘要

摘要: 非酒精性脂肪性肝病发病率逐年上升，其治疗手段有限，对其发病机制的研究是当前热点。为了更好地阐明其发病机制，迫切需要开发先进、安全、有效的体外模型或体内模型，以了解并制订针对该疾病的治疗策略。本文回顾了目前常用于非酒精性脂肪性肝病临床前研究的体外模型，并讨论了其各自的优缺点，为研究非酒精性脂肪性肝病发病机制及治疗提供理论依据。
- 非酒精性脂肪性肝病 /
- 模型, 理论 /
- 病理过程 /
- 治疗学
Abstract: The incidence rate of nonalcoholic fatty liver disease (NAFLD) is increasing year by year, with limited treatment methods, and its pathogenesis is a research hotspot at present. In order to better clarify its pathogenesis, it is urgent to develop advanced, safe, and effective in vitro or in vivo models to understand and develop treatment strategies for this disease. This article reviews the in vitro models commonly used in the preclinical study of NAFLD and discusses their advantages and disadvantages, so as to provide a theoretical basis for the pathogenesis and treatment of NAFLD.
- Non-alcoholic Fatty Liver Disease /
- Models, Theoretical /
- Pathologic Processes /
- Therapeutics

HTML全文

参考文献(44)

[1]	OVERI D, CARPINO G, FRANCHITTO A, et al. Hepatocyte injury and hepatic stem cell niche in the progression of non-alcoholic steatohepatitis[J]. Cells, 2020, 9(3): 590. DOI: 10.3390/cells9030590.
[2]	LIU W, BAKER RD, BHATIA T, et al. Pathogenesis of nonalcoholic steatohepatitis[J]. Cell Mol Life Sci, 2016, 73(10): 1969-1987. DOI: 10.1053/j.gastro.2016.02.066.
[3]	ULLAH R, RAUF N, NABI G, et al. Role of nutrition in the pathogenesis and prevention of non-alcoholic fatty liver disease: Recent updates[J]. Int J Biol Sci, 2019, 15(2): 265-276. DOI: 10.7150/ijbs.30121.
[4]	IPSEN DH, TVEDEN-NYBORG P. Extracellular vesicles as drivers of non-alcoholic fatty liver disease: Small particles with big impact[J]. Biomedicines, 2021, 9(1): 93. DOI: 10.3390/biomedicines 9010093.
[5]	PAN X, QUEIROZ J, HUSSAIN MM. Nonalcoholic fatty liver disease in CLOCK mutant mice[J]. J Clin Invest, 2020, 130(8): 4282-4300. DOI: 10.1172/JCI132765.
[6]	KIM WR, LAKE JR, SMITH JM, et al. OPTN/SRTR 2016 annual data report: Liver[J]. Am J Transplant, 2018, 18(Suppl 1): 172-253. DOI: 10.1111/ajt.14559.
[7]	TILG H, ADOLPH TE, MOSCHEN AR. Multiple parallel hits hypothesis in nonalcoholic fatty liver disease: Revisited after a decade[J]. Hepatology, 2021, 73(2): 833-842. DOI: 10.1002/hep.31518.
[8]	WILLEBRORDS J, PEREIRA IV, MAES M, et al. Strategies, models and biomarkers in experimental non-alcoholic fatty liver disease research[J]. Prog Lipid Res, 2015, 59: 106-125. DOI: 10.1016/j.plipres.2015.05.002.
[9]	HUANG F, ZHAO S, YU F, et al. Protective effects and mechanism of meretrix meretrix oligopeptides against nonalcoholic fatty liver disease[J]. Mar Drugs, 2017, 15(2): 31. DOI: 10.3390/md15020031.
[10]	ZEILINGER K, FREYER N, DAMM G, et al. Cell sources for invitro human liver cell culture models[J]. Exp Biol Med (Maywood), 2016, 241(15): 1684-1698. DOI: 10.1177/1535370216657448.
[11]	SORET PA, MAGUSTO J, HOUSSET C, et al. In vitro and in vivo models of non-alcoholic fatty liver disease: A critical appraisal[J]. J Clin Med, 2020, 10(1): 36. DOI: 10.3390/jcm10010036.
[12]	HE WX, YANG JY, XU YJ, et al. Establishment and evaluation of a fructose-induced hepatic steatosis cell model[J]. Chin Hepatol, 2019, 24(6): 638-642. DOI: 10.3969/j.issn.1008- 1704.2019.06.018. 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[J]. 肝脏, 2019, 24(6): 638-642. DOI: 10.3969/j.issn.1008-1704.2019.06.018.
[13]	JU L, SUN Y, XUE H, et al. CCN1 promotes hepatic steatosis and inflammation in non-alcoholic steatohepatitis[J]. Sci Rep, 2020, 10(1): 3201. DOI: 10.1038/s41598-020-60138-8.
[14]	ZHOU L, TANG J, YANG X, et al. Five constituents in psoralea corylifolia L. Attenuate palmitic acid-induced hepatocyte injury via inhibiting the protein kinase c-α/nicotinamide-adenine dinu cleotide phosphate oxidase pathway[J]. Front Pharmacol, 2020, 10: 1589. DOI: 10.3389/fphar.201 9.01589.
[15]	WILLEBRORDS J, PEREIRA IV, MAES M, et al. Strategies, models and biomarkers in experimental non-alcoholic fatty liver disease research[J]. Prog Lipid Res, 2015, 59: 106-125. DOI: 10.1016/j.plipres.2015.05.002.
[16]	LUO Y, HE XP, LI X, et al. Establishment and comparative analysis of several kinds of cell fatty degeneration model[J]. Chin Arch Tradit Chin Med, 2017, 35(8): 2074-2077. DOI: 10.13193/j.issn.1673-7717.2017.08.040. 罗燕, 和兴萍, 李雪, 等. 几种细胞脂肪变性模型的建立与比较分析[J]. 中华中医药学刊, 2017, 35(8): 2074-2077. DOI: 10.13193/j.issn.1673-7717.2017.08.040.
[17]	ANINAT C, PITON A, GLAISE D, et al. Expression of cytochromes P450, conjugating enzymes and nuclear receptors in human hepatoma HepaRG cells[J]. Drug Metab Dispos, 2006, 34(1): 75-83. DOI: 10.1124/dmd.105.006759.
[18]	HU C, LI L. In vitro culture of isolated primary hepatocytes and stem cell-derived hepatocyte-like cells for liver regeneration[J]. Protein Cell, 2015, 6(8): 562-574. DOI: 10.1007/s13238-015-0180-2.
[19]	ROBINTON DA, DALEY GQ. The promise of induced pluripotent stem cells in research and therapy[J]. Nature, 2012, 481(7381): 295-305. DOI: 10.1038/nature10761.
[20]	DEEPAK HB, SHREEKRISHNA N, SAMEERMAHMOOD Z, et al. An in vitro model of hepatic steatosis using lipid loaded induced pluripotent stem cell derived hepatocyte like cells[J]. J Biol Methods, 2020, 7(3): e135. DOI: 10.14440/jbm.2020.330.
[21]	WONG VW, ADAMS LA, de LÉDINGHEN V, et al. Noninvasive biomarkers in NAFLD and NASH - current progress and future promise[J]. Nat Rev Gastroenterol Hepatol, 2018, 15(8): 461-478. DOI: 10.1038/s41575-018-0014-9.
[22]	LYALL MJ, CARTIER J, THOMSON JP, et al. Modelling non-alcoholic fatty liver disease in human hepatocyte-like cells[J]. Philos Trans R Soc Lond B Biol Sci, 2018, 373(1750): 20170362. DOI: 10.1098/rstb.2017.0362.
[23]	MAZZOLENI G, DI LORENZO D, STEIMBERG N. Modelling tissues in 3D: The next future of pha rmaco-toxicology and food research?[J]. Genes Nutr, 2009, 4: 13-22. DOI: 10.1007/s12263-008-0107-0.
[24]	GREEN CJ, PRAMFALK C, MORTEN KJ, et al. From whole body to cellular models of hepatic triglyceride metabolism: Man has got to know his limitations[J]. Am J Physiol Endocrinol Metab, 2015, 308(1): E1-E20. DOI: 10.1152/ajpendo.00192.2014.
[25]	KRAUSE P, SAGHATOLISLAM F, KOENIG S, et al. Maintaining hepatocyte differentiation in vitro through co-culture with hepatic stellate cells[J]. In Vitro Cell Dev Biol Anim, 2009, 45: 205-212. DOI: 10.1016/j.stem.2018.05.027.
[26]	BARBERO-BECERRA VJ, GIRAUDI PJ, CHÁVEZ-TAPIA NC, et al. The interplay between hepatic stellate cells and hepatocytes in an in vitro model of NASH[J]. Toxicol In Vitro, 2015, 29(7): 1753-1758. DOI: 10.1016/j.tiv.2015.07.010.
[27]	ANFUSO B, GIRAUDI PJ, TIRIBELLI C, et al. Silybin modulates collagen turnover in an in vitro model of NASH[J]. Molecules, 2019, 24(7): 280. DOI: 10.3390/molecules24071280.
[28]	JAIN MR, GIRI SR, BHOI B, et al. Dual PPARα/γ agonist saroglitazar improves liver histopathology and biochemistry in experimental NASH models[J]. Liver Int, 2018, 38(6): 1084-1094. DOI: 10.1111/liv.13634.
[29]	BALE SS, GOLBERG I, JINDAL R, et al. Long-term coculture strategies for primary hepatocytes and liver sinusoidal endothelial cells[J]. Tissue Eng Part C Methods, 2015, 21(4): 413-422. DOI: 10.1089/ten.TEC.2014.0152.
[30]	KOZYRA M, JOHANSSON I, NORDLING Å, et al. Human hepatic 3D spheroids as a model for steatosis and insulin resistance[J]. Sci Rep, 2018, 8(1): 14297. DOI: 10.1038/s41598-018-32722-6.
[31]	MUKHERJEE S, ZHELNIN L, SANFIZ A, et al. Development and validation of an in vitro 3D model of NASH with severe fibrotic phenotype[J]. Am J Transl Res, 2019, 11(3): 1531-1540. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6456529/
[32]	PINGITORE P, SASIDHARAN K, EKSTRAND M, et al. Human multilineage 3D spheroids as a model of liver steatosis and fibrosis[J]. Int J Mol Sci, 2019, 20(7): 1629. DOI: 10.3390/ijms20071629.
[33]	HURRELL T, KASTRINOU-LAMPOU V, FARDELLAS A, et al. Human liver spheroids as a model to study aetiology and treatment of hepatic fibrosis[J]. Cells, 2020, 9(4): 964. DOI: 10.3390/cells 9040964.
[34]	KIM J, KOO BK, KNOBLICH JA. Human organoids: Model systems for human biology and medicine[J]. Nat Rev Mol Cell Biol, 2020, 21(10): 571-584. DOI: 10.1038/s41580-020-0259-3.
[35]	OUCHI R, TOGO S, KIMURA M, et al. Modeling steatohepatitis in humans with pluripotent stem cell-derived organoids[J]. Cell Metab, 2019, 30: 374-384. e6. DOI: 10.1016/j.cmet.2019.05. 007.
[36]	KRUITWAGEN HS, OOSTERHOFF LA, VERNOOIJ I, et al. Long-term adult feline liver organoid cultures for disease modeling of hepatic steatosis[J]. Stem Cell Reports, 2017, 8(4): 822-830. DOI: 10.1016/j.stemcr.2017.02.015.
[37]	HAAKER MW, KRUITWAGEN HS, VAANDRAGER AB, et al. Identification of potential drugs for treatment of hepatic lipidosis in cats using an in vitro feline liver organoid system[J]. J Vet Intern Med, 2020, 34: 132-138. DOI: 10.1016/j.stemcr.2017.02.015.
[38]	WANG Y, WANG H, DENG P, et al. Modeling human nonalcoholic fatty liver disease (NAFLD) with an organoids-on-a-chip system[J]. ACS Biomater Sci Eng, 2020, 6(10): 5734-5743. DOI: 10.1021/acsbiomaterials.0c00682.
[39]	WANG L, QIU YL, WANG JS. Advances in research and application of liver organoids[J]. J Clin Hepatol, 2019, 35(10): 2342-2345. DOI: 10.3969/j.issn.1001-5256.2019.10.047. 王利, 丘倚灵, 王建设. 肝类器官研究及应用进展[J]. 临床肝胆病杂志, 2019, 35(10): 2342-2345. DOI: 10.3969/j.issn.1001-5256.2019.10.047.
[40]	GORI M, SIMONELLI MC, GIANNITELLI SM, et al. Investigating nonalcoholic fatty liver disease in a liver-on-a-chip microfluidic device[J]. PLoS One, 2016, 11(7): e0159729. DOI: 10.1371/journal.pone.0159729.
[41]	LEE SY, SUNG JH. Gut-liver on a chip toward an in vitro model of hepatic steatosis[J]. Biotechnol Bioeng, 2018, 115(11): 2817-2827. DOI: 10.1002/bit.26793.
[42]	FREAG MS, NAMGUNG B, GHERARDI E, et al. Human nonalcoholic steatohepatitis on a chip[J]. Hepatol Commun, 2020, 5(2): 217-233. DOI: 10.1002/adbi.201900104.
[43]	PALMA E, DOORNEBAL EJ, CHOKSHI S. Precision-cut liver slices: A versatile tool to advance liver research[J]. Hepatol Int, 2019, 13(1): 51-57. DOI: 10.1007/s12072-018-9913-7.
[44]	PRINS GH, LUANGMONKONG T, OOSTERHUIS D, et al. A pathophysiological model of non-alcoholic fatty liver disease using precision-cut liver slices[J]. Nutrients, 2019, 11(3): 507. DOI: 10.3390/nu11030507.