Maguire T A, Swanton J G, Temple D J, Fairweather I
J Pharmacol Methods. 1984 Dec;12(4):265-83. doi: 10.1016/0160-5402(84)90013-5.
A modified technique of in situ rat-liver perfusion has been developed. Minor modifications were made for practical purposes to an existing technique including: the use of sterile Krebs Henseleit buffer to reduce contamination of perfusion medium which inhibits perfusion rate at the end of a perfusion period; the use of erythrocytes from 5-10-day-old whole human blood to provide a lysis-free oxygen-carrying component of the perfusion medium; the introduction of a sampling and flow-rate device into the reservoir that allows repetitive and accurate monitoring of hepatic blood flow (+/- 0.1 ml/min) and also simplifies sampling of venous hepatic blood; a magnetic support for the hepatic portal vein cannula to provide an easily adjustable yet firm support for the cannula and thus reduce the risk of damage to the vessel wall. Various physiological parameters of the model were investigated. These include: bile flow rate; bile acid content of bile; K+, Na+, and Ca++ content of bile; percent of a bromosulphophthalein dose excreted; oxygen consumption of perfused livers; phenytoin disposition; glycogen content; acid phosphatase activity; and the fine structure of hepatocytes. These parameters were compared with literature and in vivo experimental values, and the results suggest that the model should be suitable for the study of metabolic drug-drug interactions occurring in the rat liver.
已开发出一种改良的大鼠原位肝灌注技术。出于实际目的，对现有技术进行了细微修改，包括：使用无菌的克雷布斯-亨塞尔特缓冲液以减少灌注培养基的污染，这种污染在灌注期结束时会抑制灌注速率；使用来自5至10日龄全血的红细胞，以提供灌注培养基中无溶血的携氧成分；在储液器中引入采样和流速装置，可重复且准确地监测肝血流量（±0.1毫升/分钟），还简化了肝静脉血的采样；为肝门静脉插管提供磁性支撑，为插管提供易于调节且稳固的支撑，从而降低血管壁受损的风险。对该模型的各种生理参数进行了研究。这些参数包括：胆汁流速；胆汁中的胆汁酸含量；胆汁中的钾、钠和钙含量；排泄的溴磺酞钠剂量百分比；灌注肝脏的耗氧量；苯妥英处置；糖原含量；酸性磷酸酶活性；以及肝细胞的精细结构。将这些参数与文献值和体内实验值进行了比较，结果表明该模型应适用于研究大鼠肝脏中发生的代谢性药物相互作用。
