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摘要: 慢加急性肝衰竭病情复杂、进展快、病死率高,其发病机制、病因等仍有待进一步研究阐明。而通过慢加急性肝衰竭动物模型的建立,不仅能为慢加急性肝衰竭的发病机制研究提供良好的基础,而且能为临床治疗提供实验依据。通过对相关文献的梳理,总结了目前常用的建立慢加急性肝衰竭动物模型的方法,包括CCl4联合脂多糖(LPS)/D-氨基半乳糖胺法、硫代乙酰胺联合LPS法、血清白蛋白法、胆管结扎术法等。通过分析各种动物模型的特点,为进一步探索更理想的动物模型提供文献基础和实验依据。Abstract: Acute-on-chronic liver failure has complex conditions, rapid progression, and a high mortality rate, and further studies are still needed to clarify its pathogenesis and etiology. The establishment of animal models for acute-on-chronic liver failure can not only provide a good basis for exploring the pathogenesis of acute-on-chronic liver failure, but also provide an experimental basis for clinical treatment. Through a literature review, this article summarizes the methods commonly used to establish the animal models of acute-on-chronic liver failure, including carbon tetrachloride combined with LPS/GaIN, thioacetamide combined with LPS, serum albumin, and bile duct ligation. This article analyzes the characteristics of various animal models, so as to provide documentary and experimental bases for further exploration of more ideal animal models.
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Key words:
- Liver Diseases /
- Acute-On-Chronic Liver Failure /
- Models, Animal
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[1] BI ZH, WANG LX, LIAN JQ. Definition, prognostic assessment, and advances in the diagnosis and treatment of acute-on-chronic liver failure[J]. J Clin Hepatol, 2022, 38( 7): 1671- 1676. DOI: 10.3969/j.issn.1001-5256.2022.07.041.毕占虎, 王临旭, 连建奇. 慢加急性肝衰竭的定义、预后评估及诊治进展[J]. 临床肝胆病杂志, 2022, 38( 7): 1671- 1676. DOI: 10.3969/j.issn.1001-5256.2022.07.041. [2] Liver Failure and Artificial Liver Group, Chinese Society of Infectious Diseases, Chinese Medical Association; Severe Liver Disease and Artificial Liver Group, Chinese Society of Hepatology, Chinese Medical Association. Guideline for diagnosis and treatment of liver failure(2018)[J]. J Clin Hepatol, 2019, 35( 1): 38- 44. DOI: 10.3969/j.issn.1001-5256.2019.01.007.中华医学会感染病学分会肝衰竭与人工肝学组, 中华医学会肝病学分会重型肝病与人工肝学组. 肝衰竭诊治指南(2018年版)[J]. 临床肝胆病杂志, 2019, 35( 1): 38- 44. DOI: 10.3969/j.issn.1001-5256.2019.01.007. [3] SHANG DB, XIANG XG. Advances in the pathogenesis and treatment of acute-on-chronic liver failure[J]. J Clin Hepatol, 2021, 37( 4): 765- 769. DOI: 10.3969/j.issn.1001-5256.2021.04.005.尚大宝, 项晓刚. 慢加急性肝衰竭的发病机制和治疗进展[J]. 临床肝胆病杂志, 2021, 37( 4): 765- 769. DOI: 10.3969/j.issn.1001-5256.2021.04.005. [4] FAN Q, LI Z. Liver transplantation for acute-on-chronic liver failure[J]. Ogran Transplant, 2022, 13( 3): 333- 337. DOI: 10.3969/j.issn.1674-7445.2022.03.008.范祺, 李照. 慢加急性肝衰竭的肝移植治疗[J]. 器官移植, 2022, 13( 3): 333- 337. DOI: 10.3969/j.issn.1674-7445.2022.03.008. [5] HASSAN HM, LI J. Prospect of animal models for acute-on-chronic liver failure: A mini-review[J]. J Clin Transl Hepatol, 2022, 10( 5): 995- 1003. DOI: 10.14218/JCTH.2022.00086. [6] LIU Y, MEYER C, XU CF, et al. Animal models of chronic liver diseases[J]. Am J Physiol Gastrointest Liver Physiol, 2013, 304( 5): G449- G468. DOI: 10.1152/ajpgi.00199.2012. [7] WANG T, JIANG H, LU GC, et al. New progress in liver toxicity of carbon tetrachloride[J]. J Toxicol, 2008, 22( 4): 324- 327. DOI: 10.16421/j.cnki.1002-3127.2008.04.013.汪涛, 姜华, 陆国才, 等. 四氯化碳肝脏毒性研究新进展[J]. 毒理学杂志, 2008, 22( 4): 324- 327. DOI: 10.16421/j.cnki.1002-3127.2008.04.013. [8] YUE SW, CHEN Z. Research progress of themodel and signaling pathways of acute liver injury[J]. J Pharm Res, 2019, 38( 1): 49- 52. DOI: 10.13506/j.cnki.jpr.2019.01.013.岳淑雯, 陈真. 急性肝损伤模型及信号通路研究进展[J]. 药学研究, 2019, 38( 1): 49- 52. DOI: 10.13506/j.cnki.jpr.2019.01.013. [9] FARGHALI H, KGALALELO KEMELO M, WOJNAROVÁ L, et al. In vitro and in vivo experimental hepatotoxic models in liver research: Applications to the assessment of potential hepatoprotective drugs[J]. Physiol Res, 2016, 65( Suppl 4): S417- S425. DOI: 10.33549/physiolres.933506. [10] ZHANG HY, WEN T, LU J, et al. Establishment of CCl4-induced chronic liver injury model in rats[J]. J Clin Hepatol, 2009, 12( 3): 161- 163, 224. DOI: 10.3969/j.issn.1672-5069.2009.03.001.张海燕, 温韬, 卢静, 等. 四氯化碳诱导大鼠慢性肝损伤模型方法的探讨[J]. 实用肝脏病杂志, 2009, 12( 3): 161- 163, 224. DOI: 10.3969/j.issn.1672-5069.2009.03.001. [11] ZHANG HY, LOU JL, LI N. Establishment of CCl4-induced liver injury model in mice[J]. Beijing Med J, 2011, 33( 3): 199- 202. DOI: 10.15932/j.0253-9713.2011.03.015.张慧芸, 娄金丽, 李宁. 四氯化碳联合D-氨基半乳糖、脂多糖诱导慢加急性肝衰竭模型的建立[J]. 北京医学, 2011, 33( 3): 199- 202. DOI: 10.15932/j.0253-9713.2011.03.015. [12] GAO A, XU YJ, LU SW, et al. Effect of fecal microbiota transplantation on intestinal flora in mice with acute-on-chronic liver failure[J]. J Clin Hepatol, 2021, 37( 6): 1379- 1385. DOI: 10.3969/j.issn.1001-5256.2021.06.031.高安, 徐玉静, 陆圣威, 等. 粪菌移植对慢加急性肝衰竭小鼠模型肠道菌群的影响[J]. 临床肝胆病杂志, 2021, 37( 6): 1379- 1385. DOI: 10.3969/j.issn.1001-5256.2021.06.031. [13] ZHANG HY, HOU W, LU J, et al. The approaches for making acute hepatic failure model on chronic hepatic damage in rat[J]. Chin J Gastroenterol Hepatol, 2009, 18( 4): 348- 351. DOI: 10.3969/j.issn.1006-5709.2009.04.021.张海燕, 侯维, 卢静, 等. 大鼠慢加急性肝衰竭模型建立的方法探讨[J]. 胃肠病学和肝病学杂志, 2009, 18( 4): 348- 351. DOI: 10.3969/j.issn.1006-5709.2009.04.021. [14] PIAO ZF, ZHAO D, ZHANG HY, et al. Study on liver histopathological features in the acute-on-chronic liver failure model rat[J]. Chin J Gastroenterol Hepatol, 2010, 19( 5): 432- 436. DOI: 10.3969/j.issn.1006-5709.2010.05.013.朴正福, 赵丹, 张海燕, 等. 大鼠慢加急性肝衰竭模型肝脏组织病理学特征研究[J]. 胃肠病学和肝病学杂志, 2010, 19( 5): 432- 436. DOI: 10.3969/j.issn.1006-5709.2010.05.013. [15] ZHU G, LIU HL, HUANG X. Study of spontaneous regression of hepatic fibrosis in rats[J]. Shanghai Med J, 2006, 29( 10): 741- 743, 764. DOI: 10.3969/j.issn.0253-9934.2006.10.017.朱纲, 刘海林, 黄欣. 实验性四氯化碳诱致的大鼠肝纤维化自发逆转研究[J]. 上海医学, 2006, 29( 10): 741- 743, 764. DOI: 10.3969/j.issn.0253-9934.2006.10.017. [16] ZHANG Q, LI Y, HAN T, et al. Comparison of current diagnostic criteria for acute-on-chronic liver failure[J]. PLoS One, 2015, 10( 3): e0122158. DOI: 10.1371/journal.pone.0122158. [17] FERNÁNDEZ J, ACEVEDO J, WIEST R, et al. Bacterial and fungal infections in acute-on-chronic liver failure: Prevalence, characteristics and impact on prognosis[J]. Gut, 2018, 67( 10): 1870- 1880. DOI: 10.1136/gutjnl-2017-314240. [18] XIANG XG, FENG DC, HWANG S, et al. Interleukin-22 ameliorates acute-on-chronic liver failure by reprogramming impaired regeneration pathways in mice[J]. J Hepatol, 2020, 72( 4): 736- 745. DOI: 10.1016/j.jhep.2019.11.013. [19] WEI XZ, FU YQ WANG H, et al. A rat model of acuted liver injury induced by thioacetamide[J]. Clin Med Eng, 2009, 16( 5): 48- 49. DOI: 10.3969/j.issn.1674-4659.2009.05.026.魏新智, 付勇强, 王珲, 等. 硫代乙酰胺建立大鼠急性肝损伤模型探讨[J]. 临床医学工程, 2009, 16( 5): 48- 49. DOI: 10.3969/j.issn.1674-4659.2009.05.026. [20] XUE G, LIU JF, YAN C, et al. Establishment of a rat model of thioacetamide induced hepatic fibrosis[J]. World Chin J Dig, 2015, 23( 12): 1937. DOI: 10.11569/wcjd.v23.i12.1937.薛改, 刘建芳, 闫成, 等. 硫代乙酰胺诱导大鼠持久性肝纤维化模型的制备[J]. 世界华人消化杂志, 2015, 23( 12): 1937- 1942. DOI: 10.11569/wcjd.v23.i12.1937. [21] de MESQUITA FC, GUIXÉ-MUNTET S, FERNÁNDEZ-IGLESIAS A, et al. Liraglutide improves liver microvascular dysfunction in cirrhosis: Evidence from translational studies[J]. Sci Rep, 2017, 7( 1): 3255. DOI: 10.1038/s41598-017-02866-y. [22] TRIPATHI DM, VILASECA M, LAFOZ E, et al. Simvastatin prevents progression of acute on chronic liver failure in rats with cirrhosis and portal hypertension[J]. Gastroenterology, 2018, 155( 5): 1564- 1577. DOI: 10.1053/j.gastro.2018.07.022. [23] BHUNCHET E, EISHI Y, WAKE K. Contribution of immune response to the hepatic fibrosis induced by porcine serum[J]. Hepatology, 1996, 23( 4): 811- 817. DOI: 10.1053/jhep.1996.v23.pm0008666336. [24] LIU XH, CHEN Y, ZHANG J, et al. Human serum albumin and A rat’s model for D-galactosamine/lipopolysaccharide induced acute-on-chronic liver failure[J]. Sci Technol Rev, 2007, 25( 18): 32- 37. DOI: 10.3321/j.issn: 1000-7857.2007.18.007.刘旭华, 陈煜, 张晶, 等. 大鼠慢加急性肝衰竭实验模型的建立及其病理机制初步研究[J]. 科技导报, 2007, 25( 18): 32- 37. DOI: 10.3321/j.issn: 1000-7857.2007.18.007. [25] LIU ZQ TAN NH, HAO RB, et al. Effects of the Wenyang Jiedu Huayu prescription on expression of IL-10/STAT3 and related factors in liver of acute-on-chronic liver failure rats[J]. Clin J Chin Med, 2023, 15( 4): 87- 92. DOI: 10.3969/j.issn.1674-7860.2023.04.016.刘子情, 谭年花, 郝若冰, 等. 温阳解毒化瘀方对慢加急性肝衰竭大鼠肝组织白细胞介素-10/信号转导因子和转录激活因子3及相关因子表达的影响[J]. 中医临床研究, 2023, 15( 4): 87- 92. DOI: 10.3969/j.issn.1674-7860.2023.04.016. [26] WANG LW, WANG LK, CHEN H, et al. Ethyl pyruvate protects against experimental acute-on-chronic liver failure in rats[J]. World J Gastroenterol, 2012, 18( 40): 5709- 5718. DOI: 10.3748/wjg.v18.i40.5709. [27] LI FF, MIAO LY, SUN H, et al. Establishment of a new acute-on-chronic liver failure model[J]. Acta Pharm Sin B, 2017, 7( 3): 326- 333. DOI: 10.1016/j.apsb.2016.09.003. [28] ZHANG T, LIU XJ, JIANG C, et al. Establishment of a rat model with the pathological characteristics of ACLF[J]. Chin J Comp Med, 2021, 31( 12): 60- 64. DOI: 10.3969/j.issn.1671-7856.2021.12.009.张涛, 刘先姜, 江澄, 等. 符合慢加急(亚急)性肝功能衰竭病理特征大鼠模型的构建[J]. 中国比较医学杂志, 2021, 31( 12): 60- 64. DOI: 10.3969/j.issn.1671-7856.2021.12.009. [29] DONG Z, LIU J, SHEN H, et al. Immune complex induced rat liver fibrosis model by intraperitoneal injection of human serum albumin[J]. Chin J Exp Clin Virol, 2006, 20( 1): 12- 15. DOI: 10.3760/cma.j.issn.1003-9279.2006.01.004.董忠, 刘瑾, 沈洪, 等. 大鼠腹腔注射人血清白蛋白免疫性肝纤维化模型的实验研究[J]. 中华实验和临床病毒学杂志, 2006, 20( 1): 12- 15. DOI: 10.3760/cma.j.issn.1003-9279.2006.01.004. [30] CONG W. Establishment of acute liver failure model in rats with slow acceleration[J]. Chin J Curr Adv Gen Surg, 2016, 19( 8): 664- 666. DOI: 10.3969/j.issn.1009-9905.2016.08.027.丛伟. 大鼠慢加急性肝衰竭模型的建立[J]. 中国现代普通外科进展, 2016, 19( 8): 664- 666. DOI: 10.3969/j.issn.1009-9905.2016.08.027. [31] ENGELMANN C, MEHTA G, TACKE F. Regeneration in acute-on-chronic liver failure-the phantom lost its camouflage[J]. J Hepatol, 2020, 72( 4): 610- 612. DOI: 10.1016/j.jhep.2020.01.003. [32] CHEN T, YANG ZY, CHOUDHURY AK, et al. Complications constitute a major risk factor for mortality in hepatitis B virus-related acute-on-chronic liver failure patients: A multi-national study from the Asia-Pacific region[J]. Hepatol Int, 2019, 13( 6): 695- 705. DOI: 10.1007/s12072-019-09992-x. [33] CUI YL, YAN F, WANG YB, et al. Nucleoside analogue can improve the long-term prognosis of patients with hepatitis B virus infection-associated acute on chronic liver failure[J]. Dig Dis Sci, 2010, 55( 8): 2373- 2380. DOI: 10.1007/s10620-010-1257-7. [34] ZHANG B, DILIHUMAER ZYE, ZHANG SY, et al. Progress on pathogenesis and medical treatment of hepatitis B virus-related chronic and acute liver failure[J/CD]. Chin J Liver Dis(Electronic Version), 2023, 15( 1): 28- 33. DOI: 10.3969/j.issn.1674-7380.2023.01.005.张斌, 迪丽胡玛尔·扎依尔, 张诗雨, 等. 乙型肝炎相关慢加急性肝衰竭发病机制及治疗进展[J/CD]. 中国肝脏病杂志(电子版), 2023, 15( 1): 28- 33. DOI: 10.3969/j.issn.1674-7380.2023.01.005.
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