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使用精密切割肝切片作为评估肝功能的体外工具。

Use of precision-cut liver slices as an in vitro tool for evaluating liver function.

作者信息

Gandolfi A J, Wijeweera J, Brendel K

机构信息

Department of Anesthesiology, University of Arizona, Tucson 85724, USA.

出版信息

Toxicol Pathol. 1996 Jan-Feb;24(1):58-61. doi: 10.1177/019262339602400108.

DOI:10.1177/019262339602400108
PMID:8839281
Abstract

Precision-cut liver slices have been developed as an in vitro tool for assessing liver viability and function and for examining hepatotoxicants. Liver slices from a variety of species (including human) are prepared using mechanical slicers that produce reproducible slices of a uniform thickness, which allows optimum exchange of nutrients, waste, and gases. Slices are incubated in dynamic systems that allow the slices to be maintained viable in culture for 1-10 days. The viability of slices can be assessed by ion content (K+, Na+ ATPase status), intermediary metabolism, energy status (ATP), respiration, biosynthetic ability, and biotransformation activity. In addition, liver tissue slices allow the opportunity for extensive microscopic evaluation (light and electron) as well as newer technologies such as confocal microscopy. Assessment of the toxic potential of a chemical can be performed after a short-term or constant exposure by evaluating the viability parameters. Liver slices have been used extensively for rank-ordering the toxicity of chemicals as well as for examining the mechanisms of liver injury. Liver slices in culture also can be used for an examination of the induction of new enzymes such as cytochrome P-450 and the expression of stress proteins or peroxisomal enzymes. Finally, liver slices offer a system for evaluating whole or cryopreserved liver as well as regeneration of liver tissue after toxic insult. Liver slices have been shown to be a valid in vitro system for examining liver function and offer a bridge between in vivo and cell culture systems.

摘要

精密肝切片已被开发为一种体外工具,用于评估肝脏活力和功能以及检测肝毒性物质。使用机械切片机可制备来自多种物种(包括人类)的肝切片,这些切片厚度均匀且可重复,有利于营养物质、废物和气体的最佳交换。切片在动态系统中孵育,可使其在培养中保持活力1至10天。切片的活力可通过离子含量(钾离子、钠离子ATP酶状态)、中间代谢、能量状态(ATP)、呼吸作用、生物合成能力和生物转化活性来评估。此外,肝组织切片为广泛的显微镜评估(光学和电子显微镜)以及共聚焦显微镜等新技术提供了机会。通过评估活力参数,可在短期或持续暴露后对化学物质的潜在毒性进行评估。肝切片已被广泛用于对化学物质的毒性进行排序以及研究肝损伤机制。培养中的肝切片还可用于检测新酶(如细胞色素P-450)的诱导以及应激蛋白或过氧化物酶体酶的表达。最后,肝切片提供了一个评估完整或冷冻保存肝脏以及有毒损伤后肝组织再生的系统。肝切片已被证明是一种用于检测肝功能的有效体外系统,并在体内和细胞培养系统之间架起了一座桥梁。

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