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肝细胞的分离与培养及其在外源化合物生化研究中的应用。

Isolation and culture of liver cells and their use in the biochemical research of xenobiotics.

作者信息

Suolinna E M

出版信息

Med Biol. 1982 Oct;60(5):237-54.

PMID:6759800
Abstract

Isolated liver cells are currently used in research on hepatic function and metabolism, e.g., in studies on the synthesis of plasma proteins, control of gluconeogenesis and metabolism of glycogen. In addition they are becoming an important tool in investigating the metabolism and action of xenobiotics, where they are used for studying basic metabolic processes as well as adverse effects such as toxicity and carcinogenicity. Liver cells are isolated by a perfusion technique, where collagenase breaks the intercellular bonds, and they are often used in suspension right after isolation. In addition both primary and long-term cultures have been obtained, but in the latter the cells soon become dedifferentiated, and are not considered representative of true hepatocytes. Even in the former type of culture the liver cells lose some of their drug-metabolizing enzymes though preserving other liver-specific functions. This review focuses on the use of liver cells in the study of xenobiotics. Despite some shortcomings such as a limited time for the investigations with one preparation and the lack of long-term cultures they are potentially a valuable in vitro model for many aspects of the metabolism of xenobiotics and their toxic and carcinogenic actions. For instance, patterns of formed metabolites, enzyme induction and carcinogenic action can be studied. In addition liver cells in culture offer a system which can be developed into a valuable tool in the short-term screening of toxic and carcinogenic chemicals.

摘要

目前,分离的肝细胞被用于肝功能和代谢的研究,例如,在血浆蛋白合成、糖异生控制和糖原代谢的研究中。此外,它们正成为研究异源生物代谢和作用的重要工具,用于研究基本代谢过程以及毒性和致癌性等不良反应。肝细胞通过灌注技术分离,胶原酶在该技术中破坏细胞间连接,并且它们通常在分离后立即以悬浮液形式使用。此外,已经获得了原代培养和长期培养物,但在长期培养中,细胞很快会去分化,并且不被认为是真正肝细胞的代表。即使在原代培养类型中,肝细胞虽然保留了其他肝脏特异性功能,但也会失去一些药物代谢酶。本综述重点关注肝细胞在异源生物研究中的应用。尽管存在一些缺点,如一次制备的研究时间有限以及缺乏长期培养物,但它们在异源生物代谢及其毒性和致癌作用的许多方面可能是一种有价值的体外模型。例如,可以研究形成的代谢物模式、酶诱导和致癌作用。此外,培养的肝细胞提供了一个系统,该系统可以发展成为短期筛选有毒和致癌化学物质的有价值工具。

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