肝性脑病动物模型研究进展*

doi:10.3969/j.issn.1672-5069.2025.02.040

Abstract

Abstract: Hepatic encephalopathy (HE) is a common complications of severe liver disease, with high recurrence rate and hard to deal with. Animal models are frequently employed in research to investigate pathophysiological mechanisms and explore potential therapeutic strategies. With advancements in modern medical technology, animal models for HE research have undergone remarkable improvements. In this review, we reviewed the latest research progress, focusing on establishment, evaluation, application, limitations, and future prospects of animal models in this field, with aiming to explore new therapeutic approaches for HE.

Key words: Hepatic encephalopathy, Animal models, Evaluation

Yang Xuemeng, Yin Donghao, Hu Jianhua. Animal models of hepatic encephalopathy[J]. Journal of Practical Hepatology, 2025, 28(2): 316-319.

References

[1] Weissenborn K. Hepatic encephalopathy: definition, clinical grading and diagnostic principles. Drugs, 2019, 79(Suppl 1): 5-9.
[2] Rose CF, Amodio P, Bajaj JS, et al. Hepatic encephalopathy: novel insights into classification, pathophysiology and therapy. J Hepatol, 2020, 73(6): 1526-1547.
[3] Bellafante D, Gioia S, Faccioli J, et al. Old and new precipitants in hepatic encephalopathy: a new look at a field in continuous evolution. J Clin Med, 2023, 12(3): 1187.
[4] Ochoa-Sanchez R,Tamnanloo F, Rose CF. Hepatic encephalopathy: from metabolic to neurodegenerative. Neurochem Res, 2021, 46(10): 2612-2625.
[5] Hadjihambi A, Arias N, Sheikh M, et al. Hepatic encephalopathy: a critical current review. Hepatol Int, 2018, 12(Suppl 1): 135-147.
[6] Thabut D, Bouzbib C, Meunier L, et al. Diagnosis and management of hepatic encephalopathy: the French recommendations. Liver Int, 2023, 43(4): 750-762.
[7] Zhai H, Zhang J, Shang D, et al. The progress to establish optimal animal models for the study of acute-on-chronic liver failure. Front Med (Lausanne), 2023, 10: 1087274.
[8] Sepehrinezhad A, Shahbazi A, Sahab Negah S, et al. Drug-induced-acute liver failure: a critical appraisal of the thioacetamide model for the study of hepatic encephalopathy. Toxicol Rep, 2021, 8: 962-970.
[9] Abdel-Rafei M, Amin MM, Hasan HF. Novel effect of daflon and low-dose γ-radiation in modulation of thioacetamide-induced hepatic encephalopathy in male albino rats. Hum Exp Toxicol, 2017, 36(1): 62-81.
[10] Tsai CY, Su CH, Chan JY, et al. Nitrosative stress-induced disruption of baroreflex neural circuits in a rat model of hepatic encephalopathy: a DTI study. Sci Rep, 2017, 7: 40111.
[11] Jia W, Liu J, Hu R, et al.Xiaochaihutang improves the cortical astrocyte edema in thioacetamide-induced rat acute hepatic encephalopathy by activating NRF2 pathway. Front Pharmacol, 2020, 11: 382.
[12] Bai Y, Wang S, Wu F, et al. The changes of mitochondria in substantianigra and anterior cerebral cortex of hepatic encephalopathy induced by thioacetamide. Anat Rec (Hoboken), 2019, 302(7): 1169-1177.
[13] Khanna A, Trigun SK.Resveratrol normalizes hyperammonemia induced proinflammatory and pro-apoptotic conditions in rat brain. Int J Complement Altern Med, 2016, 4: 00115.
[14] 郑鋆. TAA诱导的A型肝性脑病大鼠肠道通透性改变及机制研究. 辽宁医学杂志, 2021, 35(05): 1-5.
[15] DeMorrow S,Cudalbu C, Davies N, et al. 2021 ISHEN guidelines on animal models of hepatic encephalopathy. Liver Int, 2021, 41(7): 1474-1488.
[16] Liu R, Kang JD, Sartor RB, et al. Neuroinflammation in murine cirrhosis is dependent on the gut microbiome and is attenuated by fecal transplant. Hepatology, 2020, 71(2): 611-626.
[17] Liu R, Ahluwalia V, Kang JD, et al. Effect of increasing age on brain dysfunction in cirrhosis. HepatolCommun, 2018, 3(1): 63-73.
[18] Vairappan B, Sundhar M, Srinivas BH. Resveratrol restores neuronal tight junction proteins through correction of ammonia and inflammation in CCl4-induced cirrhotic mice. Mol Neurobiol, 2019, 56(7): 4718-4729.
[19] Haeger P, Bouchet A,Ossandon C, et al. Treatment with melatonin improves cognitive behavior and motor skills in a rat model of liver fibrosis. Ann Hepatol, 2019, 18(1): 101-108.
[20] 逄菲, 胡瑾华. 肝性脑病的动物模型及分子生物学机制研究进展. 国际消化病杂志, 2014, 34: 84-86.
[21] Gonçalves DF, Tassi CC, Amaral GP, et al. Effects of caffeine on brain antioxidant status and mitochondrial respiration in acetaminophen-intoxicated mice.Toxicol Res (Camb), 2020, 9(5): 726-734.
[22] Saad MA,Rastanawi AA, El-Yamany MF. Alogliptin abates memory injuries of hepatic encephalopathy induced by acute paracetamol intoxication via switching-off autophagy-related apoptosis. Life Sci, 2018, 215: 11-21.
[23] Vigo MB, Pérez MJ, De Fino F, et al. Acute acetaminophen intoxication induces direct neurotoxicity in rats manifested as astrogliosis and decreased dopaminergic markers in brain areas associated with locomotor regulation.Biochem Pharmacol, 2019, 170: 113662.
[24] Heidari R,Jamshidzadeh A, Niknahad H, et al. Effect of taurine on chronic and acute liver injury: focus on blood and brain ammonia. Toxicol Rep, 2016, 3: 870-879.
[25] McGill MR, Williams CD, Xie Y, et al. Acetaminophen-induced liver injury in rats and mice: comparison of protein adducts, mitochondrial dysfunction, and oxidative stress in the mechanism of toxicity.Toxicol Appl Pharmacol, 2012, 264(3): 387-394.
[26] 何巧燕, 王知平, 王芳. 龙胆苦苷对D-氨基半乳糖联合脂多糖诱导的慢性肝损伤模型小鼠的保护作用. 山西中医药大学学报, 2022, 23(03): 168-172.
[27] Cauli O, González-Usano A, Cabrera-Pastor A, et al. Blocking NMDA receptors delays death in rats with acute liver failure by dual protective mechanisms in kidney and brain. Neuromolecular Med, 2014, 16(2): 360-375.
[28] Megaraj V, Ding X, Fang C, et al. Role of hepatic and intestinal p450 enzymes in the metabolic activation of the colon carcinogen azoxymethane in mice. Chem Res Toxicol, 2014, 27(4): 656-662.
[29] McMillin MA, Frampton GA, Seiwell AP, et al. TGFβ1 exacerbates blood-brain barrier permeability in a mouse model of hepatic encephalopathy via upregulation of MMP9 and downregulation of claudin-5. Lab Invest, 2015, 95(8): 903-913.
[30] Rose C, Michalak A, Pannunzio M, et al. Mild hypothermia delays the onset of coma and prevents brain edema and extracellular brain glutamate accumulation in rats with acute liver failure. Hepatology, 2000, 31(4): 872-877.
[31] Kristiansen RG, Lindal S, Myreng K, et al. Neuropathological changes in the brain of pigs with acute liver failure. Scand J Gastroenterol, 2010, 45(7-8): 935-943.
[32] Gandhi CR, Murase N, Subbotin VM, et al. Portacaval shunt causes apoptosis and liver atrophy in rats despite increases in endogenous levels of major hepatic growth factors. J Hepatol, 2002, 37(3): 340-348.

Animal models of hepatic encephalopathy

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