Chauvin M F, Bolon C, Conjard A, Martin G, Ferrier B, Martin M, Michoudet C, Durozard D, Laréal M C, Gauthier C, Simonnet H, Elhamri M, Dugelay S, Joly B, Baverel G
Laboratoire de Physiopathologie Métabolique et Rénale, INSERM CRI 950201, Faculté de Médecine R. Laënnec, Lyon, France.
Cell Biol Toxicol. 1996 Dec;12(4-6):283-7. doi: 10.1007/BF00438159.
Among the cellular models used in in vitro renal pharmacotoxicology, isolated kidney tubules, used as suspensions mainly of proximal tubules, offer important advantages. They can be prepared in large amounts under nonsterile conditions within 1-2 h; thus, it is possible to employ a great number of experimental conditions simultaneously and to obtain rapidly many experimental results. Kidney tubules can be prepared from the kidney of many animal species and also from the human kidney; given the very limited availability of healthy human renal tissue, it is therefore possible to choose the most appropriate species for the study of a particular problem encountered in man. Kidney tubules can be used for screening and prevention of nephrotoxic effects and to identify their mechanisms as well as to study the renal metabolism of xenobiotics. When compared with cultured renal cell, a major advantage of kidney tubules is that they remain differentiated. The main limitations of the use of kidney tubules in pharmacotoxicology are (1) the necessity to prepare them as soon as the renal tissue sample is obtained; (2) their limited viability, which is restricted to 2-3 h; (3) the inability to expose them chronically to a potential nephrotoxic drug; (4) the inability to study transepithelial transport; and (5) the uncertainty in the extrapolation to man of the results obtained using animal kidney tubules. These advantages and limitations of the use of human and animal kidney tubules in pharmacotoxicology are illustrated mainly by the results of experiments performed with valproate, an antiepileptic and moderately hyperammonemic agent. The fact that kidney tubules, unlike cultured renal cells, retain key metabolic properties is also shown to be of the utmost importance in detecting certain nephrotoxic effects.
在体外肾脏药物毒理学中使用的细胞模型中，分离的肾小管（主要作为近端肾小管悬浮液使用）具有重要优势。它们可以在非无菌条件下于1-2小时内大量制备；因此，可以同时采用大量实验条件并迅速获得许多实验结果。肾小管可以从多种动物的肾脏以及人类肾脏中制备；鉴于健康人类肾脏组织的可用性非常有限，因此可以选择最适合的物种来研究人类遇到的特定问题。肾小管可用于筛选和预防肾毒性作用、确定其机制以及研究外源性物质的肾脏代谢。与培养的肾细胞相比，肾小管的一个主要优势是它们保持分化状态。在药物毒理学中使用肾小管的主要局限性在于：（1）必须在获得肾脏组织样本后尽快制备；（2）其生存能力有限，仅限于2-3小时；（3）无法将它们长期暴露于潜在的肾毒性药物；（4）无法研究跨上皮转运；（5）将使用动物肾小管获得的结果外推至人类时存在不确定性。在药物毒理学中使用人类和动物肾小管的这些优势和局限性主要通过使用丙戊酸盐（一种抗癫痫且中度引起高氨血症的药物）进行的实验结果来说明。与培养的肾细胞不同，肾小管保留关键代谢特性这一事实在检测某些肾毒性作用方面也被证明至关重要。
