Wauthier Valérie, Verbeeck Roger K, Buc Calderon Pedro
Unité de Pharmacocinétique, Métabolisme, Nutrition, et Toxicologie (PMNT), Département des Sciences Pharmaceutiques, Université Catholique de Louvain, 73 Avenue Mounier, 1200 Bruxelles, Belgium.
Toxicol In Vitro. 2004 Dec;18(6):879-85. doi: 10.1016/j.tiv.2004.04.013.
Precision-cut liver slices (PCLS) offer a lot of advantages because all heterogeneity and cell-cell interactions within the original tissue matrix are maintained. This in vitro model was used to study the effect of ageing on certain aspects of drug metabolism and liver function in young (3 months), adult (9 months) and old (24 months) Wistar male rats. Protein synthesis, an important liver function, was not modified in young, adult and old rats, suggesting that ageing does not impair liver functionality but it affects some specific targets. Among them, a decrease in total P450 in liver microsomes and the loss of CYP3A23 inducibility in PCLS were clearly observed in old rats as compared to adult rats. Finally, the amount of total paracetamol conjugates was not modified between 9 and 24 months but in old rats, sulfoconjugation of paracetamol, its major route of elimination, was decreased.
精密肝切片（PCLS）具有诸多优势，因为其保留了原始组织基质内的所有异质性和细胞间相互作用。该体外模型用于研究衰老对年轻（3个月）、成年（9个月）和老年（24个月）雄性Wistar大鼠药物代谢和肝功能某些方面的影响。蛋白质合成是一项重要的肝功能，在年轻、成年和老年大鼠中未发生改变，这表明衰老不会损害肝脏功能，但会影响一些特定靶点。其中，与成年大鼠相比，老年大鼠肝脏微粒体中总P450明显减少，PCLS中CYP3A23诱导性丧失。最后，9至24个月期间对乙酰氨基酚结合物总量未发生改变，但在老年大鼠中，对乙酰氨基酚的主要消除途径——硫酸结合作用减少。
