Efficacy of Double Filtration Plasmapheretic Cross Circulation with a High Permeability Membrane using Whole Liver on Porcine Fulminant Hepatic Failure Model

使用全肝的高渗透性膜双重过滤血浆交叉循环对猪暴发性肝衰竭模型的功效

• 批准号: 13671272
• 负责人: TOTSUKA Eishi
• 金额: $ 0.9万
• 依托单位: Hirosaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671272/
• 关键词: Bioartificial liver; Plasmapheresis; Semipermeable membrane; Fulminant hepatic failure; 摘出肝異種交叉灌流; ブタ; 交差灌流

In the use of bioartificial liver devices, preparation of sufficient liver cell mass to provide adequate metabolic support, reduction of xenogeneic immune reaction, and avoidance of viral transmission are required. We developed a plasmapheresis using semipermeable membrane combined with whole liver perfusion (PMWLP) system, which offered a large number of functional liver cells, an immunoprotection, and a barrier to the viral transmission. The effect of the PMWLP system in porcine FHF model was investigated. Porcine FHF model was established by the intraportal administration of alpha-amanitin and lipopolysaccharide. Nine hours after the drugs injection, the FHF pigs were connected to the PMWLP system for 6 hours (n=5). In control pigs (n=10), the circuit was not connected to the porcine whole liver. Animal survival was significantly longer in the PMWLP treated pigs. Although the control pigs developed hypotension progressively, the PMWLP treated pigs demonstrated a cardiovascular stabilization. The PMWLP treatment significantly suppressed the elevation of liver enzymes, total bile acid, ammonia, and metionine. The degrees of hepatocyte necrosis and neutrophil infiltration were remarkably lessened in the PMWLP treated pigs. The PMWLP system prolonged animal survival, prevented cardiovascular instability, attenuated liver injury, enhanced bile acid metabolism, and decreased the hepatic encephalopathy related agents.

在使用生物人工肝装置时，需要制备足够的肝细胞团以提供足够的代谢支持，减少异种免疫反应，并避免病毒传播。我们开发了半渗透膜血浆置换结合全肝灌注系统（PMWLP），它提供了大量的功能性肝细胞，免疫保护和病毒传播的屏障。研究了PMWLP系统在猪FHF模型中的作用。通过门静脉注射α-鹅膏蕈碱和脂多糖建立猪FHF模型。在药物注射后9小时，将FHF猪连接到PMWLP系统6小时（n=5）。在对照猪（n=10）中，回路未连接至猪全肝。在PMWLP处理的猪中，动物存活期显著延长。尽管对照组猪逐渐出现低血压，但PMWLP处理组猪显示心血管稳定。PMWLP治疗显著抑制了肝酶、总胆汁酸、氨和甲硫氨酸的升高。PMWLP处理的猪中肝细胞坏死和中性粒细胞浸润的程度显著减轻。PMWLP系统延长动物存活，防止心血管不稳定，减轻肝损伤，增强胆汁酸代谢，并减少肝性脑病相关因子。

项目成果

Nozaki T, Totsuka E, Takiguchi M, et al.: "Attenuation of canine hepatic warm ischemia/reperfusion injury by nitric oxide donor, FK409"Hirosaki Med J. (印刷中). (2003)

Nozaki T、Totsuka E、Takiguchi M 等人：“一氧化氮供体 FK409 减轻犬肝热缺血/再灌注损伤”Hirosaki Med J.（出版中）。

Totsuka E, Itoh S, Suzuki K, et al.: "Usefulness of redox tolerance test in evaluating fatty liver"Hepato-Gastroenterol. 48. 184-187 (2001)

Totsuka E、Itoh S、Suzuki K 等人：“氧化还原耐受试验在评估脂肪肝中的有用性”肝胃肠道。

Totsuka E, Itoh S, Suzuki K, et al.: "Usefulness of redox to lerance test in evaluating fatty liver"Hepato-Gastroenterol. 48. 184-187 (2001)

Totsuka E、Itoh S、Suzuki K 等人：“氧化还原耐受试验在评估脂肪肝中的有用性”肝胃肠病学。

Nara M, Hakamada K, Totsuka E, et al.: "Efficacy of double filtration plasmapheretic cross-circulation using a high permeability membrane between totally hepatectomized dogs and donor pigs"Transplantation. 72. 1736-1742 (2001)

Nara M、Hakamada K、Totsuka E 等人：“在完全肝切除的狗和供体猪之间使用高渗透性膜进行双重过滤血浆层交叉循环的功效”移植。