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[体外肝细胞毒性损伤研究的模型系统]

[Model systems for study of toxic injury of hepatocytes in vitro].

作者信息

Kucera Otto, Lotková Halka, Kriváková Pavla, Rousar Tomás, Cervinková Zuzana

机构信息

Ustav fyziologie, Univerzita Karlova v Praze, Lékarská fakulta v Hradci Králové.

出版信息

Cesk Fysiol. 2006;55(3):103-10.

Abstract

The liver is a common target of toxic effect of a number of xenobiotics, which is in particular a result of its central role in intermediary and energetic metabolism and in biotransformation processes. Ethical, economic, legislative, research and other reasons do not allow testing all of newly-synthesized compounds in in vivo conditions. Hence new methods and approaches for hepatotoxicity testing in vitro have been developing. The most important systems for study of toxicity and metabolic activity in vitro are isolated perfused liver, liver slices, isolated liver cells in suspensions or in primary cultures including co-culture methods and special 3D techniques, various subcellular fractions and stabilised cell lines. These models can be used for cytotoxicity and genotoxicity screening, evaluation of potential hepatoprotective capacity of different compounds, study of toxic injury and characterization of hepatotoxicity mechanisms. Currently there is no an ideal in vitro liver model system for testing of hepatotoxic substances in vitro, nevertheless use of these model systems reduces economic costs and ethic and legislative problems. Model systems in vitro afford opportunity to study in detail mechanisms of hepatotoxicity in comparison with in vivo conditions. Definition of their actual advantages and disadvantages allows choosing a suitable model system for study of particular problem. We cannot imagine current research of liver toxicity without using these model sytems.

摘要

肝脏是多种异生物素毒性作用的常见靶点,这尤其归因于其在中间代谢、能量代谢及生物转化过程中的核心作用。出于伦理、经济、立法、研究及其他方面的原因,无法在体内条件下对所有新合成的化合物进行测试。因此,体外肝毒性测试的新方法和新途径不断涌现。体外研究毒性和代谢活性的最重要体系包括离体灌注肝脏、肝切片、悬浮或原代培养的分离肝细胞(包括共培养方法和特殊的三维技术)、各种亚细胞组分以及稳定的细胞系。这些模型可用于细胞毒性和遗传毒性筛选、评估不同化合物的潜在肝保护能力、研究毒性损伤以及表征肝毒性机制。目前尚无用于体外测试肝毒性物质的理想体外肝脏模型系统,不过使用这些模型系统可降低经济成本,并避免伦理和立法问题。与体内条件相比,体外模型系统为详细研究肝毒性机制提供了机会。明确其实际的优缺点有助于为特定问题的研究选择合适的模型系统。不使用这些模型系统,我们就无法想象当前的肝脏毒性研究。

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