Milkiewicz P, Mills C O, Hubscher S G, Cardenas R, Cardenas T, Williams A, Elias E
Liver Research Laboratories, Queen Elizabeth Hospital, Edgbaston, Birmingham, UK.
J Hepatol. 2001 Jan;34(1):4-10. doi: 10.1016/s0168-8278(00)00076-3.
BACKGROUND/AIMS: Lysyl fluorescein conjugated bile acid analogues (LFCBAA) closely parallel their natural counterparts. To assess LFCBAA as a tool for the visualization of bile acid transport within liver tissue.
Wistar rats were administered physiological concentrations of the primary bile acid analogue cholyllysyl fluoroscein (CLF) and of the secondary bile acid analogue lithocholyllysyl fluorescein (LLF) and serial liver biopsies were taken at fixed intervals. Both compounds were also injected retrogradely into the biliary tree. Frozen sections were examined by fluorescence microscopy.
Both CLF and LLF were rapidly taken up from sinusoidal blood but differed significantly in their hepatic handling. CLF was rapidly transported into bile, whereas LLF transport was slower and produced significantly more bile duct fluorescence. LLF clearance showed a lobular gradient with last remaining bile acid being confined largely to zone 3. Both compounds were avidly taken up by cholangiocytes after injection intravenously or retrogradely into the biliary tree.
Visualization of LFCBAA by fluorescence microscopy may yield further information regarding hepatobiliary bile acid localization during studies of physiological and pathological mechanisms involved in transport of bile acids. The presence of both compounds within cholangiocytes strongly suggests that they may undergo a degree of chole-hepatic recirculation.
背景/目的：赖氨酸荧光素结合胆汁酸类似物（LFCBAA）与它们的天然对应物非常相似。评估LFCBAA作为可视化肝组织内胆汁酸转运工具的可行性。
给Wistar大鼠给予生理浓度的初级胆汁酸类似物胆酰赖氨酸荧光素（CLF）和次级胆汁酸类似物石胆酰赖氨酸荧光素（LLF），并在固定间隔进行系列肝脏活检。这两种化合物也逆行注入胆管树。通过荧光显微镜检查冰冻切片。
CLF和LLF均迅速从窦状隙血液中摄取，但它们在肝脏处理过程中有显著差异。CLF迅速转运到胆汁中，而LLF的转运较慢，且产生的胆管荧光明显更多。LLF清除呈现小叶梯度，最后剩余的胆汁酸主要局限于3区。静脉注射或逆行注入胆管树后，胆管细胞均能 avidly摄取这两种化合物。
在研究胆汁酸转运的生理和病理机制过程中，通过荧光显微镜观察LFCBAA可能会获得有关肝胆胆汁酸定位的更多信息。胆管细胞内同时存在这两种化合物强烈表明它们可能经历一定程度的肠肝循环。 （注：avidly这个词原文可能有误，推测是actively，这里暂按原文翻译）
