Villanger O, Bjørnbeth B A, Lyberg T, Raeder M G
Institute for Experimental Medical Research, University of Oslo, Norway.
Scand J Gastroenterol. 1995 Dec;30(12):1186-93. doi: 10.3109/00365529509101629.
This study was undertaken to elucidate why large bilirubin loads cause canalicular cholestasis and whether bile acid infusions protect against bilirubin-induced cholestasis.
The effects of bilirubin infusion on canalicular bile secretion and canalicular membrane morphology were studied in bile acid-depleted pigs (BADP), bile acid-primed pigs (BAPP), and pigs co-infused with bile acids during bilirubin loading (BACIP).
Bilirubin caused complete cholestasis in BADP, 38% bile flow reduction in BAPP, and no effect on bile flow in BACIP. Scanning electron micrographs showed loss of 70% of canalicular microvilli in BADP, 13% loss and pathologic changes in the remaining 75% of microvilli in BAPP, and no canalicular changes in BACIP. Cholestasis was not due to hydromechanical obstruction of bile ductules or bile Ca2+ depletion.
Bilirubin causes cholestasis in BADP by injuring canalicular microvilli. Intravenous glycocholate infusions fully protect the liver against bilirubin-induced cholestasis and canalicular microvillar injury.
本研究旨在阐明大量胆红素负荷导致胆小管胆汁淤积的原因，以及胆汁酸输注是否能预防胆红素诱导的胆汁淤积。
在胆汁酸耗竭猪（BADP）、胆汁酸预处理猪（BAPP）以及在胆红素负荷期间同时输注胆汁酸的猪（BACIP）中，研究胆红素输注对胆小管胆汁分泌和胆小管膜形态的影响。
胆红素导致BADP出现完全性胆汁淤积，使BAPP胆汁流量减少38%，而对BACIP的胆汁流量无影响。扫描电子显微镜照片显示，BADP中70%的胆小管微绒毛丧失，BAPP中13%的微绒毛丧失，其余75%的微绒毛出现病理改变，而BACIP中胆小管无变化。胆汁淤积并非由于胆小管的流体力学阻塞或胆汁中钙离子耗竭所致。
胆红素通过损伤胆小管微绒毛在BADP中导致胆汁淤积。静脉输注甘氨胆酸盐可完全保护肝脏免受胆红素诱导的胆汁淤积和胆小管微绒毛损伤。
