Shattuck K E, Grinnell C D, Rassin D K
University of Texas Medical Branch, Department of Pediatrics, Galveston 77550.
JPEN J Parenter Enteral Nutr. 1994 Mar-Apr;18(2):119-27. doi: 10.1177/0148607194018002119.
The intravenous infusion of amino acid solutions has been associated with cholestatic liver injury in hospitalized patients and in laboratory animals. In the isolated rat liver, we recently showed that the acute decrease in bile flow, previously reported by other investigators, is dose related, reversible, and associated with dose-related increases in total biliary amino acid concentrations. In the present study, we characterized the effects of graded infusions of amino acid solutions, with and without taurocholate, on biliary secretion of individual amino acids and glutathione, an important regulator of bile flow. Livers from young adult male rats were perfused with an amino acid solution for 1 hour and allowed to recover for 30 minutes. Infusion of the amino acid solution was associated with dose-related increases in biliary concentrations of most amino acids included in the amino acid solution. Infusion of amino acid solutions resulted in a decreased bile/perfusate ratio of most amino acids, which were secreted into bile in amounts approximating their calculated uptake from the infusate. The inclusion of taurocholate in the infusate was associated with lower biliary concentrations of each individual amino acid and significant decreases in biliary total, reduced, and oxidized glutathione. Further investigation of the relationship between these changes in biliary amino acids and glutathione concentrations and the cholestasis associated with infusion of amino acid solutions may provide insights into the mechanism by which amino acids induce such cholestasis.
在住院患者和实验动物中，静脉输注氨基酸溶液已被证实与胆汁淤积性肝损伤有关。在离体大鼠肝脏实验中，我们最近发现，其他研究者先前报道的胆汁流量急性减少与剂量相关、具有可逆性，且与胆汁中总氨基酸浓度的剂量相关增加有关。在本研究中，我们研究了在有或没有牛磺胆酸盐的情况下，分级输注氨基酸溶液对单个氨基酸和谷胱甘肽（胆汁流量的重要调节因子）胆汁分泌的影响。用氨基酸溶液灌注成年雄性幼鼠的肝脏1小时，然后使其恢复30分钟。输注氨基酸溶液与氨基酸溶液中所含大多数氨基酸的胆汁浓度呈剂量相关增加有关。输注氨基酸溶液导致大多数氨基酸的胆汁/灌注液比率降低，这些氨基酸分泌到胆汁中的量接近其从灌注液中计算得出的摄取量。在灌注液中加入牛磺胆酸盐会导致每种单个氨基酸的胆汁浓度降低，以及胆汁中总谷胱甘肽、还原型谷胱甘肽和氧化型谷胱甘肽显著减少。进一步研究胆汁中氨基酸和谷胱甘肽浓度的这些变化与输注氨基酸溶液相关的胆汁淤积之间的关系，可能会为氨基酸诱导这种胆汁淤积的机制提供见解。
