Veel T, Villanger O, Holthe M R, Skjørten F S, Raeder M G
University of Oslo, Institute for Experimental Medical Research, Ullevaal Hospital, Norway.
Acta Physiol Scand. 1991 Dec;143(4):421-9. doi: 10.1111/j.1748-1716.1991.tb09254.x.
To examine whether intravenous bilirubin infusion causes cholestasis and impairs liver metabolism, bile secretion and ethanol clearance were measured in 34 anaesthetized pigs before and after intravenous infusion of 0.5 mumol kg-1 min-1 bilirubin for 4.5 hours. Bilirubin infusion increased plasma bilirubin to 556 +/- 76 mumol l-1 and hepatic tissue bilirubin to 3.5 +/- 1.3 mmol kg tissue weight-1. Bilirubin infusion depressed bilirubin secretion and net hepatic uptake of cholate and taurocholate, and caused a 86 +/- 6% reduction of cholate-induced bile secretion. Bilirubin caused formation of large cytoplasmic vacuoles in hepatocytes and dilatation of bile canaliculi. Ethanol clearance and secretin-dependent ductular bile secretion were unaffected by bilirubin. We conclude that intravenous infusion of unconjugated bilirubin causes accumulation of bilirubin in the liver, vacuolization of the hepatocyte cytoplasm and canalicular but not ductular cholestasis. The canalicular cholestasis is not due to impaired hepatic mitochondrial energy metabolism, but may be due to inhibition of a common pathway for lipid, bilirubin and bile salt secretion from hepatocytes.
为研究静脉输注胆红素是否会导致胆汁淤积并损害肝脏代谢，在34只麻醉猪静脉输注0.5 μmol·kg⁻¹·min⁻¹胆红素4.5小时前后，对胆汁分泌和乙醇清除率进行了测量。输注胆红素后，血浆胆红素升高至556±76 μmol·L⁻¹，肝组织胆红素升高至3.5±1.3 mmol·kg组织重量⁻¹。输注胆红素会抑制胆红素分泌以及肝脏对胆酸盐和牛磺胆酸盐的净摄取，并使胆酸盐诱导的胆汁分泌减少86±6%。胆红素导致肝细胞内形成大量细胞质空泡以及胆小管扩张。乙醇清除率和促胰液素依赖性小叶间胆管胆汁分泌不受胆红素影响。我们得出结论，静脉输注未结合胆红素会导致胆红素在肝脏中蓄积，肝细胞质空泡化以及胆小管而非小叶间胆管胆汁淤积。胆小管胆汁淤积并非由于肝脏线粒体能量代谢受损，而可能是由于抑制了肝细胞分泌脂质、胆红素和胆汁盐的共同途径。
