Bolder U, Ton-Nu H T, Schteingart C D, Frick E, Hofmann A F
Department of Medicine, University of California at San Diego, La Jolla, USA.
Gastroenterology. 1997 Jan;112(1):214-25. doi: 10.1016/s0016-5085(97)70238-5.
BACKGROUND & AIMS: In sepsis, intrahepatic cholestasis occurs frequently, suggesting impaired hepatocyte transport of bile acids and organic anions. The aim of the study was to define the magnitude, time course, and the site of impaired biliary secretion in a rat sepsis model.
Maximal transport for two bile acids (cholyltaurine and chenodeoxycholyltaurine) and two organic anions (sulfobromophthalein and sulfolithocholyltaurine) was measured in isolated perfused livers at various times after lipopolysaccharide injection. Basolateral and canalicular liver plasma membrane vesicles were used to characterize the impairment in hepatocyte transport.
Maximal hepatocyte transport was reduced for all compounds by 60%-81% compared with controls. Bile acid-independent bile flow was reduced by 51%. Impairment was maximal 12 hours after endotoxin injection and recovered thereafter. In basolateral plasma membrane vesicles, sodium-dependent transport for bile acids was reduced by 36%-47%. Sodium-independent transport of organic anions was reduced by 40%-55%. Adenosine triphosphate-stimulated transport was greatly decreased in canalicular vesicles prepared from endotoxemic animals for all four compounds probably because of a reduced number of transport molecules, based on kinetic studies.
Basolateral and canalicular bile acid and organic anion transport are markedly impaired in endotoxemia. These mechanisms may contribute to the cholestasis of sepsis.
在脓毒症中，肝内胆汁淤积频繁发生，提示肝细胞对胆汁酸和有机阴离子的转运受损。本研究的目的是确定大鼠脓毒症模型中胆汁分泌受损的程度、时间进程及部位。
在注射脂多糖后的不同时间，测量分离灌注肝脏中两种胆汁酸（胆酰牛磺酸和鹅脱氧胆酰牛磺酸）和两种有机阴离子（磺溴酞钠和磺石胆酰牛磺酸）的最大转运量。利用基底外侧和胆小管肝细胞膜囊泡来表征肝细胞转运的损伤情况。
与对照组相比，所有化合物的最大肝细胞转运量降低了60%-81%。不依赖胆汁酸的胆汁流量降低了51%。损伤在注射内毒素后12小时达到最大程度，此后恢复。在基底外侧细胞膜囊泡中，胆汁酸的钠依赖性转运降低了36%-47%。有机阴离子的非钠依赖性转运降低了40%-55%。基于动力学研究，内毒素血症动物制备的胆小管囊泡中，三磷酸腺苷刺激的所有四种化合物的转运均大幅降低，可能是因为转运分子数量减少。
在内毒素血症中，基底外侧和胆小管的胆汁酸及有机阴离子转运明显受损。这些机制可能导致脓毒症的胆汁淤积。
