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具有肝小叶样结构的混合人工肝模块对肝衰竭大鼠的评估。

Evaluation of a hybrid artificial liver module with liver lobule-like structure in rats with liver failure.

作者信息

Aoki K, Mizumoto H, Nakazawa K, Funatsu K, Kajiwara T

机构信息

Department of Chemical Engineering, Faculty of Engineering, Kyushu University, Fukuoka - Japan.

出版信息

Int J Artif Organs. 2008 Jan;31(1):55-61. doi: 10.1177/039139880803100108.

DOI:10.1177/039139880803100108
PMID:18286455
Abstract

We studied the recovery of rats with fulminant hepatic failure (FHF) by treating them with our original hybrid artificial liver support system (HALSS). We developed an original artificial liver module having a liver lobule-like structure (LLS). This module consists of many hollow fibers regularly arranged in close proximity and hepatocyte aggregates (organoids) induced into the extra capillary space of the module by centrifugal force. The LLS module can express some liver specific functions at high levels and maintain them for several months in vitro. In this study, we evaluated the efficacy of our LLS-HALSS by using rats with FHF induced by a method that combined partial hepatectomy with hepatic ischemia. In the animal experiments, blood ammonia levels rapidly increased in the control group (sham-HALSS group). These rats died during or immediately after application of the sham-HALLS. On the other hand, in the LLS module application group (LLS-control group), the increase in blood ammonia was completely suppressed and all rats recovered. Blood constituents at 4 weeks after application were at normal levels, and the weight of the liver was the same as that of a normal rat. These results indicate that HALSS may be useful for treating liver failure patients until liver transplantation can be performed or until regeneration of the native liver occurs.

摘要

我们使用我们最初的混合人工肝支持系统(HALSS)治疗暴发性肝衰竭(FHF)大鼠,研究其恢复情况。我们开发了一种具有肝小叶样结构(LLS)的原始人工肝模块。该模块由许多紧密排列的中空纤维和通过离心力诱导到模块毛细血管外空间的肝细胞聚集体(类器官)组成。LLS模块能够高水平表达一些肝脏特异性功能,并在体外维持数月。在本研究中,我们通过使用部分肝切除术联合肝缺血诱导FHF的大鼠,评估了我们的LLS - HALSS的疗效。在动物实验中,对照组(假HALSS组)血氨水平迅速升高。这些大鼠在应用假HALSS期间或之后立即死亡。另一方面,在LLS模块应用组(LLS - 对照组)中,血氨升高被完全抑制,所有大鼠均恢复。应用后4周的血液成分处于正常水平,肝脏重量与正常大鼠相同。这些结果表明,HALSS可能对治疗肝衰竭患者有用,直到能够进行肝移植或直到天然肝脏发生再生。

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