Development of intralobular bile ductules after spontaneous hepatitis in Long-Evans mutant rats.
Development of intralobular bile ductules after spontaneous hepatitis in Long-Evans mutant rats.
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Long-Evans 突变大鼠自发性肝炎后小叶内胆管的发育。
DOI：
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发表时间：
1996
期刊：
影响因子：
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通讯作者：
M. Sakurai
中科院分区：
文献类型：
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作者：
H. Betto;K. Kaneda;T. Yamamoto;A. Kojima;M. Sakurai
长埃文斯肉桂 (LEC) 大鼠自发性肝炎期间发生卵圆细胞增殖。据报道，卵圆细胞在癌变过程中通过小肝细胞分化为成熟肝细胞。本研究旨在证明LEC大鼠体内卵圆细胞向肝小叶中典型胆管细胞的分化以及小叶内胆管形成的特征。我们通过传统光学和电子显微镜、细胞角蛋白免疫染色和 3 维重建分析，检查了 LEC 大鼠肝脏中肝前期、急性肝炎、慢性肝炎和癌前期阶段的卵圆细胞、小肝细胞和胆管细胞的动力学、小叶内分布和形态。我们的结果表明，在出生后 20 至 23 周的急性肝炎期间，卵圆细胞增殖并延伸到肝小叶的门静脉周围区。它们表现出管状结构，管腔轮廓不明确，基底膜不完整。黄疸缓解后，第 26 周时，小肝细胞与卵圆细胞一起增殖，并在汇管区占主导地位。 28～30周的慢性肝期，管状结构转变为典型的胆小管，管腔清晰，基底膜完整，小肝细胞大小恢复正常。小叶内胆管起源于小叶间胆管，走行于Disse间隙，在走行中产生数个分支，终止于肝细胞。目前的结果表明，自发性肝炎后LEC大鼠肝小叶中增殖的卵圆细胞不仅分化为小肝细胞，而且分化为典型的胆管细胞。这项研究表明，小叶内胆管可能在卵圆细胞和小肝细胞紊乱增殖期间和之后维持胆汁排泄方面发挥作用。
Oval cell proliferation occurs during spontaneous hepatitis in Long-Evans cinnamon (LEC) rats. It has been reported that oval cells undergo differentiation into mature hepatocytes via small hepatocytes during carcinogenesis. This study was designed to demonstrate in vivo differentiation of oval cells into typical bile ductular cells in the liver lobule and the characteristic feature of intralobular bile ductule formation in LEC rats. We have examined kinetics, intralobular distribution, and morphology of oval cells, small hepatocytes, and bile ductular cells in LEC rat livers at prehepatitic, acute hepatitic, chronic hepatitic, and precancerous stages by conventional light and electron microscopy, immunostaining for cytokeratin, and 3-dimensional reconstruction analysis. Our results indicate that oval cells proliferated and extended into the periportal zone of the liver lobule during acute hepatitis at 20 to 23 weeks after birth. They exhibited tubular structures with a poorly defined lumen and incomplete basement membrane. After remission of the jaundice, small hepatocytes proliferated in association with oval cells and predominated in the periportal zone at 26 weeks. In a chronic hepatitic stage at 28 to 30 weeks, tubular structures were transformed into typical bile ductules, which had a well defined lumen and complete basement membrane, and small hepatocytes became a normal size. Intralobular bile ductules originated from the interlobular bile ducts, ran in the space of Disse, giving rise to several branches in the course, and were terminated at the hepatocytes. The present results indicate that oval cells that proliferate in the liver lobule of LEC rats after spontaneous hepatitis not only differentiate into small hepatocytes but also into typical bile ductular cells. This study suggests that intralobular bile ductules may play roles in maintaining the bile excretion during and after the disorganized proliferation of oval cells and small hepatocytes.