SEQUENTIAL APPEARANCE OF INTESTINAL MUCOSAL CELL-TYPES IN THE RIGHT AND CAUDATE LIVER LOBES OF FURAN-TREATED RATS
SEQUENTIAL APPEARANCE OF INTESTINAL MUCOSAL CELL-TYPES IN THE RIGHT AND CAUDATE LIVER LOBES OF FURAN-TREATED RATS
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DOI：
10.1016/0270-9139(92)90018-5
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发表时间：
1992-11-01
期刊：
影响因子：
13.5
通讯作者：
SIRICA, AE
中科院分区：
文献类型：
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作者：
ELMORE, LW;SIRICA, AE
呋喃在大鼠肝脏中迅速诱导肠化生和相关胆管纤维化的独特、叶特异性发展模式。为了建立这种胆管纤维化发生中的早期细胞-前体关系，进行了一项时程研究，其中年轻成年雄性Fisher 344大鼠在32天的治疗期内通过管饲法接受每日剂量为45 mg/kg体重的呋喃。对呋喃给药期间不同时间点从这些动物获得的单个肝叶的分析显示了以下顺序的组织病理学变化，其主要位于右侧肝叶，在较小程度上位于尾状肝叶：第1天，3区严重肝坏死延伸到肝腺泡的2区;第3 - 5天，肝坏死区出现弥漫性炎性细胞浸润，逐渐消退;第7天，组织切片中出现明显的胆管增生，显示正常肝实质明显丧失;第9天，增生的胆管组织继续取代损伤的肝脏，现在偶尔含有由柱状嗜碱性上皮细胞组成的化生腺结构;第12 - 16天，发育中的化生腺体细胞多样性增加，杯状细胞相继出现，Paneth细胞和降钙素阳性神经内分泌细胞;第32天，典型的胆管纤维化，由增生的胆管型结构定义，与化生肠腺数量增加和进行性更致密的纤维化基质相关。有趣的是，在16和32天，肝中新形成的化生肠腺的细胞组成与正常成年大鼠小肠中的Lieberkuhn隐窝的细胞组成非常相似。这些结果强烈表明，增生的胆管细胞分化优先沿着小肠粘膜谱系在右肝和尾状肝叶的呋喃治疗的大鼠。此外，他们支持小肠化生是肝内胆管纤维化发展的重要中间体的观点。
Furan rapidly induces in rat liver a unique, lobe-specific pattern of development of intestinal metaplasia and associated cholangiofibrosis. To establish early cell-precursor relationships in the genesis of this cholangiofibrosis, a time-course study was conducted in which young adult male Fisher 344 rats received furan by gavage at a daily dose of 45 mg/kg body wt over a 32-day treatment period. An analysis of individual liver lobes obtained at different time points from these animals during furan treatment revealed the following sequence of histopathological changes, which were located mainly in the right and, to a lesser extent, the caudate liver lobes: day 1, severe hepatonecrosis in zone 3 extending into zone 2 of the liver acini; days 3 to 5, presence of a diffuse inflammatory cell infiltrate in hepatonecrotic areas, which gradually resolved; day 7, prominent bile ductule hyperplasia in tissue sections exhibiting marked loss of normal liver parenchyma; day 9, continued replacement of injured liver by hyperplastic bile ductule tissue, which now contained occasional metaplastic glandular structures composed of columnar basophilic epithelial cells; days 12 to 16, increasing cell diversity in the developing metaplastic glands, with the sequential appearance of goblet cells, Paneth cells and serotonin-positive neuroendocrine cells; and day 32, typical cholangiofibrosis defined by hyperplastic bile ductule-type structures in association with an increased number of metaplastic intestinal glands and progressively more dense fibrotic stroma. Interestingly, at 16 and 32 days the cellular composition of the newly formed metaplastic intestinal glands in liver closely resembled that of the crypts of Lieberkuhn in the normal adult rat small intestine. These results strongly suggest that hyperplastic bile ductule cells differentiate preferentially along the small-intestinal mucosa lineage in the right and caudate liver lobes of the furan-treated rats. In addition, they support the view that small intestinal metaplasia is an important intermediate in the development of cholangiofibrosis in liver.