Abernathy C O, Zimmerman H J, Ishak K G, Utili R, Gillespie J
Office of Water, United States Environmental Protection Agency, Washington, DC 20406.
Proc Soc Exp Biol Med. 1992 Jan;199(1):54-8. doi: 10.3181/00379727-199-43328.
Chlorpromazine at a concentration of 250 microM and estradiol-17 beta-D-glucuronide at 17.5 microM on infusion led to a sharp reduction in bile flow by the in vitro perfused rat liver. This was accompanied by fragmentation and a loss of canalicular microvilli, dilatation of canaliculi, and thickening of pericanalicular ectoplasm. Less prominent were the smooth endoplasmic reticulum dilatation, lysosomal lamination, and the appearance of amorphous bile in hepatocyte cytoplasm. The bile flow and electron microscopy appearance were restored to normal by infusion of tauroursodeoxycholate in a concentration of 5 mumols/min for the estradiol-17 beta-D-glucuronide-induced cholestasis and 1.5 mumol/min for the chlorpromazine-induced cholestasis. Changes in ultrastructure paralleled changes in bile flow. These observations demonstrate the feasibility of electron microscopy studies on the perfused liver, and the rapidity with which cholestatic changes appear.
在体外灌注大鼠肝脏实验中，浓度为250微摩尔的氯丙嗪和17.5微摩尔的雌二醇 - 17β - D - 葡萄糖醛酸苷在输注时导致胆汁流量急剧减少。这伴随着胆小管微绒毛的断裂和丢失、胆小管扩张以及胆小管周围胞质增粗。滑面内质网扩张、溶酶体分层以及肝细胞胞质中出现无定形胆汁的现象则不太明显。对于雌二醇 - 17β - D - 葡萄糖醛酸苷诱导的胆汁淤积，以5微摩尔/分钟的浓度输注牛磺熊去氧胆酸可使胆汁流量和电子显微镜下的表现恢复正常；对于氯丙嗪诱导的胆汁淤积，以1.5微摩尔/分钟的浓度输注可使其恢复正常。超微结构的变化与胆汁流量的变化平行。这些观察结果证明了对灌注肝脏进行电子显微镜研究的可行性，以及胆汁淤积性变化出现的快速性。
