Bhathal P S, Jordan T W, Mackay I R
Department of Anatomical Pathology, Royal Melbourne Hospital, Victoria, Australia.
Liver. 1990 Aug;10(4):193-204. doi: 10.1111/j.1600-0676.1990.tb00459.x.
Biliary tract injury was examined in four inbred strains of mice orally dosed with 500 micrograms of the fungal toxin sporidesmin. Semiquantitative histological analysis was used to assess the grade of necroinflammatory changes in the gall bladder, intra- and extrahepatic biliary tree and lobular parenchyma. Injury was greatest in the C57BL/6 and C3H strain mice and was least in SJL/J mice. In these strains injury was greatest at 4 days and had regressed by 10 days. In BALB/c mice the damage, although similar to that in SJL/J mice at 4 days, persisted at the same severity at day 10 and was accompanied by periductal fibrosis and occasionally by obliteration of ducts typical of sclerosing cholangitis. Analysis of the time-course of development of the lesions in C57BL/6 mice showed that the primary target for the toxin is the biliary epithelium. The severity of the lesions within the liver increased centripetally and the worst affected ducts were found at the confluence of the lobar ducts with the common bile duct. The variation in the degree of damage and rate of healing between strains may be due to differences in sporidesmin excretion in bile or interactions with biliary epithelial cells and/or efficacy of protective cellular repair mechanisms.
对口服500微克真菌毒素柄曲霉素的四种近交系小鼠进行了胆道损伤检查。采用半定量组织学分析来评估胆囊、肝内和肝外胆管以及小叶实质的坏死性炎症变化程度。C57BL/6和C3H品系小鼠的损伤最严重，而SJL/J小鼠的损伤最轻。在这些品系中，损伤在第4天最严重，到第10天有所消退。在BALB/c小鼠中，虽然损伤在第4天时与SJL/J小鼠相似，但在第10天时仍保持相同的严重程度，并伴有导管周围纤维化，偶尔还会出现典型的硬化性胆管炎的导管闭塞。对C57BL/6小鼠病变发展的时间进程分析表明，毒素的主要靶标是胆管上皮。肝脏内病变的严重程度向心性增加，在叶间胆管与胆总管汇合处发现受影响最严重的导管。不同品系之间损伤程度和愈合速度的差异可能是由于柄曲霉素在胆汁中的排泄差异、与胆管上皮细胞的相互作用和/或保护性细胞修复机制的功效不同。
