Department of Hepatobiliary Surgery II, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Guangzhou Clinical Research and Transformation Center for Artificial Liver, Institute of Regenerative Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
State Key Laboratory of Organ Failure Research, Southern Medical University, Guangzhou, Guangdong, China.
Int J Artif Organs. 2023 Mar;46(3):141-152. doi: 10.1177/03913988221145501. Epub 2023 Jan 4.
Acute liver failure (ALF) is a severe liver disease with high morbidity and mortality rates. Animal models are important for research on ALF. This study aimed to establish a reproducible, Tibetan miniature pig model of D-galactosamine-induced ALF and verify it using a dual plasma molecular adsorption system (DPMAS).
Tibet miniature pigs were randomly divided into four groups (A, B, C, D) after catheterization. D-galactosamine (D-gal) at 0.45, 0.40, 0.35, and 0.35 g/kg body weight, respectively, was injected through the catheter. Group D was treated with DPMAS 48 h after D-gal administration. Vital signs and blood index values were recorded every 12 h after D-gal administration. H&E, TUNEL, Ki67, and Masson staining tests were performed.
After D-gal administration, Tibetan miniature pigs developed different degrees of debilitation, loss of appetite, and jaundice. Survival times of groups A, B, C, and D were 39.7 ± 5.9, 53.0 ± 12.5,61.3 ± 8.1, and 61 ± 7 h, respectively. Blood levels of ALT, AST, TBIL, ammonia, PT, and inflammation factors significantly increased compared with baseline levels in the different groups (s < 0.05). Pathological results revealed a clear liver cell necrosis positive correlation with D-gal dose. However, DPMAS did not increase the survival time in ALF, ammonia, or liver cell necrosis.
We successfully established a reproducible Tibetan miniature pig model of d-galactosamine-induced ALF, and we believe that a dosage of 0.35 g/kg is optimal.
急性肝衰竭（ALF）是一种高发病率和死亡率的严重肝脏疾病。动物模型对于 ALF 的研究很重要。本研究旨在建立一种可重现的、藏酋猴诱导的急性肝衰竭模型，并使用双重血浆分子吸附系统（DPMAS）对其进行验证。
在导管插入后，将藏酋猴随机分为四组（A、B、C、D）。分别通过导管注射 0.45、0.40、0.35 和 0.35 g/kg 体重的 D-半乳糖胺（D-gal）。D 组在 D-gal 给药后 48 小时接受 DPMAS 治疗。在 D-gal 给药后每 12 小时记录生命体征和血液指标值。进行 H&E、TUNEL、Ki67 和 Masson 染色试验。
D-gal 给药后，藏酋猴出现不同程度的虚弱、食欲不振和黄疸。A、B、C 和 D 组的存活时间分别为 39.7±5.9、53.0±12.5、61.3±8.1 和 61±7 h。与不同组的基线水平相比，ALT、AST、TBIL、氨、PT 和炎症因子的血液水平显著升高（s<0.05）。病理结果显示，肝细胞坏死与 D-gal 剂量呈明显正相关。然而，DPMAS 并未增加 ALF、氨或肝细胞坏死的存活时间。
我们成功建立了一种可重现的藏酋猴 D-半乳糖胺诱导的急性肝衰竭模型，我们认为 0.35 g/kg 的剂量是最佳的。
