EARLY CHANGES IN BILE-DUCT LINING CELLS AND HEPATOCYTES IN RATS TREATED WITH ALPHA-NAPHTHYLISOTHIOCYANATE
EARLY CHANGES IN BILE-DUCT LINING CELLS AND HEPATOCYTES IN RATS TREATED WITH ALPHA-NAPHTHYLISOTHIOCYANATE
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DOI：
10.1016/0041-008x(88)90121-4
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发表时间：
1988-04-01
影响因子：
3.8
通讯作者：
HINTON, RH
中科院分区：
文献类型：
--
作者：
CONNOLLY, AK;PRICE, SC;HINTON, RH
300 mg/kg体重α处理后，大鼠胆管内壁细胞形态学改变先于肝细胞形态学改变。-naphthylisothocyanate(雕像)。给药4小时后，电镜显示胆管扩张，胆管上皮细胞的微绒毛丢失，一些咬管上皮细胞之间的紧密连接明显开放。这些变化在6小时后更为明显，一些胆管内衬细胞出现核膜脱离和内质网空泡化。ANIT治疗6小时后光镜显示一些门静脉水肿和γ γ丢失。-谷氨酰转肽酶活性来自胆管内壁细胞。治疗后8小时，许多胆管明显受损，形成胆塞，细胞脱落进入胆管。治疗24小时后，大部分胆管被破坏，但48小时后有一些再生的迹象。治疗4、6、8小时后，光镜下肝实质细胞未见组织改变。在超微结构水平上，治疗后6小时可见肝细胞间紧密连接的改变。在此时间点之前未观察到其他变化。治疗24小时后，实质出现局灶性坏死。γ的测定。胆汁中-谷氨酰转肽酶和白蛋白的结果与胆管内衬细胞活性丧失和肝细胞间紧密连接减弱的组织化学证据一致。
Morphological changes in bile duct lining cells preceded morphological changes in hepatocytes in rats treated with 300 mg/kg body wt of .alpha.-naphthylisothocyanate (ANIT). Four hours after dosing, electron microscopy showed dilation of bile ducts, loss of microvilli from bile duct epithelial cells, and an apparent opening of the tight junctions between some bite duct epithelial cells. These changes were more pronounced after 6 hr and there was in some bile duct lining cells detachment of the nuclear membrane and vacuolation of the endoplasmic reticulum. Light microscopy 6 hr after treatment with ANIT showed some portal edema and loss of .gamma.-glutamyl transpeptidase activity from the bile duct lining cells. By 8 hr after treatment many ducts showed clear-cut damage, with bile plugs forming and cells exfoliating into the ducts. Twenty-four hours after treatment the majority of bile ducts were destroyed but by 48 hr there was some evidence of regeneration. No tissue changes were seen at the light microscopy level in the liver parenchymal cells 4, 6, or 8 hr after treatment. At the ulstructural level some alterations in the tight junctions between hepatocytes were seen 6 hr after treatment. No other changes were observed before this time point. By 24 hr after treatment there was focal necrosis in the parenchyma. Assay of .gamma.-glutamyl transpeptidase and albumin in bile gave results consistent with the histochemical evidence for the loss of activity from bile duct lining cells and for weakening of the tight junctions between hepatocytes.