Reversal of experimental acute hepatic failure in the rat.
Reversal of experimental acute hepatic failure in the rat.
复制标题
逆转大鼠实验性急性肝衰竭。
DOI：
10.1016/0022-4804(80)90016-5
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发表时间：
1980
期刊：
影响因子：
--
通讯作者：
M. J. Phillips
中科院分区：
文献类型：
--
作者：
L. Makowka;R. Falk;L. Rotstein;J. Falk;N. Nossal;B. Langer;L. Blendis;M. J. Phillips
采用选择性肝毒素盐酸半乳糖胺建立了大鼠急性暴发性肝衰竭动物模型。给Lewis大鼠腹腔注射2.6 g/kg的剂量可导致可重复的、潜在可逆的肝坏死和高死亡率。该模型探讨了同基因肝细胞、异体肝细胞和骨髓分散的单细胞悬浮液为肝脏恢复提供“支持”的能力。同系肝细胞（4 × 107细胞）在毒素给药后48和60小时腹腔注射，使存活率分别提高到70%和66%，而对照组为0%。与Lewis菌株在次要组织相容性位点不同的Fischer菌株制备的肝细胞同样提高了存活率（62.5%）。毒素给药24小时后腹腔注射同基因骨髓细胞（4 × 107个细胞）使存活率提高到62.5%，而对照组为0%。这种作用不是由成熟的巨噬细胞或淋巴细胞群介导的，而是特定于来自骨髓的细胞，因为脾细胞、胸腺细胞和腹膜渗出细胞的单细胞悬液对增加存活率没有影响。肝细胞和骨髓细胞的作用机制以及它们的作用机制是相同的还是不同的仍有待确定。细胞移植可能为治疗急性肝衰竭提供一种新的简便方法。
A suitable animal model of acute fulminant hepatic failure was developed in the rat by the administration of the selective hepatotoxin, galactosamine hydrochloride. A dosage of 2.6 g/kg given intraperitoneally to Lewis rats resulted in reproducible, potentially reversible hepatic necrosis and high mortality. The ability of dispersed single-cell suspensions of syngeneic hepatocytes, allogeneic hepatocytes, and bone marrow to provide “support” so that liver recovery could occur was explored in this model. Syngeneic hepatocytes (4 × 107cells) given intraperitoneally 48 and 60 hr after toxin administration increased survival to 70 and 66%, respectively, compared to a control of 0%. Hepatocytes prepared from Fischer strain animals which differ from Lewis strain at minor histocompatibility loci similarly improved survival (62.5%). Syngeneic bone marrow cells (4 × 107cells) given intraperitoneally 24 hr after toxin administration improved survival to 62.5% compared to a control group of 0%. This effect is not mediated by a mature macrophage or lymphoid cell population, but is specific to the cells derived from bone marrow, since single-cell suspensions of splenocytes, thymocytes, and peritoneal exudate cells had no effect on increasing survival. The mechanism of action of hepatocytes and bone marrow cells and whether they act by the same or different mechanisms remain to be defined. Cellular transplantation may offer a new simple measure in the treatment of acute hepatic failure.