Экспериментальные модели печеночно-клеточной недостаточности на основе изолированного и комбинированного действия этиологических факторов
Ключевые слова:
печень, сочетанные поражения печени, экспериментальные модели, неалкогольная жировая болезнь печени, алкогольная болезнь печени, лекарственные поражения печени, in vivo, in vitro
Аннотация
Заболевания печени продолжают оставаться одной из ведущих причин смертности среди хронических патологий во всем мире. Особая сложность в лечении возникает из-за наличия у пациентов нескольких этиологических факторов, которые приводят к формированию сочетанных поражений печени. В связи с этим возрастает потребность в создании экспериментальных моделей, имитирующих данную клиническую ситуацию. Такие модели позволяют воспроизводить комбинированные метаболические, токсические и инфекционные воздействия в условиях, максимально приближенных к клинической практике. В данной статье представлен обзор существующих экспериментальных моделей сочетанных поражений печени, а также изолированных форм, которые служат основой для изучения патогенеза и разработки эффективных терапевтических стратегий.
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Литература
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35. Du Y., Broering R., Li X., et al. In Vivo Mouse Models for Hepatitis B Virus Infection and Their Application. Front Immunol. 2021;12:766534. doi: 10.3389/fimmu.2021.766534.
36. Dong R., Zhang B., Zhang X. Liver organoids: an in vitro 3D model for liver cancer study. Cell Biosci. 2022;12(1):152. doi: 10.1186/s13578-022-00890-8.
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2. Devarbhavi H., Asrani S.K., Arab J.P., et al. Global burden of liver disease: 2023 update. J Hepatol. 2023;79(2):516-537. doi: 10.1016/j.jhep.2023.03.017.
3. Cheemerla S., Balakrishnan M. Global Epidemiology of Chronic Liver Disease. Clin Liver Dis (Hoboken). 2021;4;17(5):365-370. doi: 10.1002/cld.1061.
4. Сандлер Ю.Г., Винницкая Е.В., Гендриксон Л.Н., и др. Аутоиммунный гепатит: как избежать ошибки? Доктор.Ру. 2017;2(131):15–21
5. Altamirano J., Miquel R., Katoonizadeh A., et al. A histologic scoring system for prognosis of patients with alcoholic hepatitis. Gastroenterology 2014;146(5):1231–1239. doi: 10.1053/j.gastro.2014.01.018.
6. Thompson W.L., Takebe T. Human liver model systems in a dish. Dev Growth Differ. 2021;63(1):47-58. doi: 10.1111/dgd.12708.
7. Крылов Д. П., Родимова С. А., Карабут М. М., Кузнецова Д. С. Экспериментальные модели для изучения структурно-функционального состояния патологической печени (обзор). Современные технологии в медицине 2023;15(4):65. doi: 10.17691/stm2023.15.4.06.
8. Akhtar A. The flaws and human harms of animal experimentation. Camb Q Healthc Ethics 2015;24(4):407–419. doi: 10.1017/s0963180115000079.
9. Мазеркина И.А. Оценка лекарственной гепатотоксичности in vitro на клеточных моделях (обзор). Безопасность и риск фармакотерапии. 2023;11(2):131-144. doi: 10.30895/2312-7821-2023-11-2-351.
10. Aoudjehane L., Gautheron J., Goff W.L., et al. Novel Defatting Strategies Reduce Lipid Accumulation in Primary Human Culture Models of Liver Steatosis. Dis. Model. Mech. 2020;13 doi: 10.1242/dmm.042663.
11. Gómez-Lechón M.J., Donato M.T., Castell J.V., Jover R. Human Hepatocytes as a Tool for Studying Toxicity and Drug Metabolism. Curr. Drug Metab. 2003;4:292–312. doi: 10.2174/1389200033489424.
12. Wilkening S., Stahl F., Bader A. Comparison of Primary Human Hepatocytes and Hepatoma Cell Line Hepg2 with Regard to Their Biotransformation Properties. Drug Metab. Dispos. 2003;31:1035–1042. doi: 10.1124/dmd.31.8.1035.
13. Zeilinger K., Freyer N., Damm G., et al. Cell Sources for in Vitro Human Liver Cell Culture Models. Exp. Biol. Med. 2016;241:1684–1698. doi: 10.1177/1535370216657448.
14. Segovia-Zafra A., Di Zeo-Sánchez D.E., López-Gómez C., et al. Preclinical models of idiosyncratic drug-induced liver injury (iDILI): moving towards prediction. Acta Pharm Sin B. 2021;11(12):3685–726. doi: 10.1016/j.apsb.2021.11.013.
15. Sison-Young R.L., Mitsa D., Jenkins R.E., at al. Comparative Proteomic Characterization of 4 Human Liver-Derived Single Cell Culture Models Reveals Significant Variation in the Capacity for Drug Disposition, Bioactivation, and Detoxication. Toxicological Sciences. 2015;147(2):412-24. doi: 10.1093/toxsci/kfv136.
16. Hu C., Li L. In Vitro Culture of Isolated Primary Hepatocytes and Stem Cell-Derived Hepatocyte-like Cells for Liver Regeneration. Protein Cell. 2015;6:562–574. doi: 10.1007/s13238-015-0180-2
17. Imagawa K., Takayama K., Isoyama S., et al. Generation of a bile salt export pump deficiency model using patient-specific induced pluripotent stem cell-derived hepatocyte-like cells. Sci Rep. 2017;7:41806. doi: 10.1038/srep41806.
18. Polli J.E. In vitro studies are sometimes better than conventional human pharmacokinetic in vivo studies in assessing bioequivalence of immediate-release solid oral dosage forms. AAPS J 2008;10(2): 289–299. doi: 10.1208/s12248-008-9027-6.
19. Gamboa J.M., Leong K.W. In vitro and in vivo models for the study of oral delivery of nanoparticles. Adv Drug Deliv Rev. 2013;15;65(6):800-10. doi: 10.1016/j.addr.2013.01.003.
20. Mackowiak B., Fu Y., Maccioni L., Gao B. Alcohol-associated liver disease. J Clin Invest. 2024;1;134(3):176345. doi: 10.1172/JCI176345.
21. Rastovic U., Bozzano S.F., Riva A., at al. Human Precision-Cut Liver Slices: A Potential Platform to Study Alcohol-Related Liver Disease. Int J Mol Sci. 2023;21;25(1):150. doi: 10.3390/ijms25010150.
22. Bertola A., Mathews S., Ki S.H., at al. Mouse model of chronic and binge ethanol feeding (the NIAAA model). Nat Protoc 2013;8(3):627–637. doi: 10.1038/nprot.2013.032.
23. Khanova E., Wu R., Wang W., et al. Pyroptosis by caspase11/4-gasdermin-D pathway in alcoholic hepatitis in mice and patients. Hepatology 2018;67(5):1737–1753. doi: 10.1002/hep.29645.
24. Tsukamoto H., French S.W., Rektelberger R.D., Largman C. Cyclical pattern of blood alcohol levels during continuous intragastric ethanol infusion in rats. Alcohol Clin Exp Res 1985;9(1): 31–37. doi: 10.1111/j.1530-0277.1985.tb05046.
25. Nawroth J.C., Petropolis D.B., Manatakis D.V., et al. Modeling Alcohol-Associated Liver Disease in a Human Liver-Chip. Cell Rep. 2021;36(3):109393. doi: 10.1016/j.celrep.2021.109393.
26. Dewyse L., Reynaert H., van Grunsven L.A. Best Practices and Progress in Precision-Cut Liver Slice Cultures. Int J Mol Sci. 2021;22(13):7137. doi: 10.3390/ijms22137137.
27. de Graaf I.A., Olinga P., de Jager M.H., et al. Preparation and incubation of precision-cut liver and intestinal slices for application in drug metabolism and toxicity studies. Nat Protoc. 2010;5(9):1540-51. doi: 10.1038/nprot.2010.111.
28. Thandra K.C., Barsouk A., Saginala K., et al. Epidemiology of non-alcoholic fatty liver disease and risk of hepatocellular carcinoma progression. Clin Exp Hepatol. 2020;6(4):289-294. doi: 10.5114/ceh.2020.102153.
29. Basaranoglu M., Neuschwander-Tetri B.A. Nonalcoholic Fatty Liver Disease: Clinical Features and Pathogenesis. Gastroenterol Hepatol (N Y). 2006;2(4):282-291.
30. Hansen B.C., Liang Z., Sun F., et al. Nonalcoholic fatty liver disease (NAFLD) in obese rhesus monkeys provides the first animal model that accurately reflects the human condition. FASEB J 2017;31(S1):895.6–895.6. doi: 10.1096/fasebj.31.1_supplement.895.6.
31. Cao L., Xu E., Zheng R., et al. Traditional Chinese medicine Lingguizhugan decoction ameliorate HFD-induced hepatic-lipid deposition in mice by inhibiting STING-mediated inflammation in macrophages. Chin Med. 2022;17(1):7. doi: 10.1186/s13020-021-00559-3.
32. Fang T., Wang H., Pan X., et al. Mouse models of nonalcoholic fatty liver disease (NAFLD): pathomechanisms and pharmacotherapies. Int J Biol Sci. 2022;18(15):5681-5697. doi: 10.7150/ijbs.65044.
33. Ishimoto T., Lanaspa M.A., Rivard C.J., et al. High-fat and high-sucrose (western) diet induces steatohepatitis that is dependent on fructokinase. Hepatology. 2013;58(5):1632-43. doi: 10.1002/hep.26594.
34. Lefere S., Puengel T., Hundertmark J., et al. Differential effects of selective- and pan-PPAR agonists on experimental steatohepatitis and hepatic macrophages. J Hepatol. 2020;73(4):757-770. doi: 10.1016/j.jhep.2020.04.025.
35. Du Y., Broering R., Li X., et al. In Vivo Mouse Models for Hepatitis B Virus Infection and Their Application. Front Immunol. 2021;12:766534. doi: 10.3389/fimmu.2021.766534.
36. Dong R., Zhang B., Zhang X. Liver organoids: an in vitro 3D model for liver cancer study. Cell Biosci. 2022;12(1):152. doi: 10.1186/s13578-022-00890-8.
37. Xu R., Hu P., Li Y., et al. Advances in HBV infection and replication systems in vitro. Virol J. 2021;18(1):105. doi: 10.1186/s12985-021-01580-6.
38. De Crignis E., Hossain T., Romal S., et al. Application of human liver organoids as a patient-derived primary model for HBV infection and related hepatocellular carcinoma. Elife. 2021;10:e60747. doi: 10.7554/eLife.60747.
39. Feng F., Zhao Y. Hepatocellular Carcinoma: Prevention, Diagnosis, and Treatment. Med Princ Pract. 2024;33(5):414-423. doi: 10.1159/000539349.
40. Sundi P.R.I.O., Thipe V.C., Omar M.A., et al. Preclinical human and murine models of hepatocellular carcinoma (HCC). Clin Res Hepatol Gastroenterol. 2024;48(7):102418. doi: 10.1016/j.clinre.2024.102418.
41. Li G., Liu D., Cooper T.K., et al. Successful chemoimmunotherapy against hepatocellular cancer in a novel murine model. J Hepatol. 2017;66(1):75-85. doi: 10.1016/j.jhep.2016.07.044.
42. Blidisel A., Marcovici I., Coricovac D., et al. Experimental Models of Hepatocellular Carcinoma-A Preclinical Perspective. Cancers (Basel). 2021;13(15):3651. doi: 10.3390/cancers13153651.
43. Asrani S.K., Devarbhavi H., Eaton J., Kamath P.S. Burden of liver diseases in the world. J Hepatol. 2019;70:151–171. doi: 10.1016/j.jhep.2018.09.014.
44. Kalligeros M., Vassilopoulos A., Vassilopoulos S., et al. Prevalence of Steatotic Liver Disease (MASLD, MetALD, and ALD) in the United States: NHANES 2017-2020. Clin Gastroenterol Hepatol. 2024;22(6):1330-1332.e4. doi: 10.1016/j.cgh.2023.11.003.
45. Buyco D.G., Martin J., Jeon S., et al. Experimental models of metabolic and alcoholic fatty liver disease. World J Gastroenterol. 2021;27(1):1-18. doi: 10.3748/wjg.v27.i1.1.
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Опубликован
27-10-2025
Как цитировать
Фоминых Ю. А., Наджафова К. Н., Жданова И. А., Молчанова М. С., Сонин Д. Л., Галагудза М. М. Экспериментальные модели печеночно-клеточной недостаточности на основе изолированного и комбинированного действия этиологических факторов // Патологическая физиология и экспериментальная терапия. 2025. Т. 69. № 4. С. 157–167.
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