Biliary secretion of endotoxin and pathogenesis of primary biliary cirrhosis.
Biliary secretion of endotoxin and pathogenesis of primary biliary cirrhosis.
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胆道内毒素的分泌与原发性胆汁性肝硬化的发病机制。
DOI：
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
K. Tanikawa
中科院分区：
文献类型：
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作者：
S. Sakisaka;H. Koga;K. Sasatomi;Y. Mimura;Toshihiro Kawaguchi;K. Tanikawa
先前的研究表明，来自肠的内毒素通过门静脉血进入肝脏，主要由枯否细胞代谢。在本研究中，荧光标记的内毒素注射到大鼠门静脉被证明不仅在枯否细胞，而且在肝细胞。胆汁中回收到大量的标记内毒素。在原发性胆汁性肝硬化（PBC）患者的肝脏中，免疫组织化学显示内毒素在胆管上皮细胞中有显著滞留，熊去氧胆酸治疗显著减少了这些细胞中的滞留。细胞凋亡检测结果显示，PBC肝组织中肝细胞和胆管上皮细胞凋亡率增加，经熊去氧胆酸处理后，胆管上皮细胞凋亡率明显降低。PBC肝脏中的免疫组织化学显示胆管上皮细胞中7H6抗原的荧光强度显著降低，表明胆管的细胞旁通透性增加，因为该抗原的细胞免疫定位已被证明与紧密连接的细胞旁通透性呈负相关。这些结果表明，在胆管上皮细胞，内毒素的保留，增加细胞凋亡，并增加紧密连接的通透性可能参与PBC的发病机制。图片Figure 1
Previous studies suggested endotoxin, derived from the intestine through the portal blood to the liver, was predominantly metabolized by Kupffer cells. In the present study, fluorescent-labeled endotoxin injected into the rat portal vein was demonstrated not only in Kupffer cells but also in hepatocytes. Furthermore a great amount of labeled endotoxin was recovered in bile. In the livers of patients with primary biliary cirrhosis (PBC), immunohistochemistry demonstrated significant retention of endotoxin in the biliary epithelial cells, and treatment with ursodeoxycholic acid significantly reduced the retention in those cells. The study for detection of apoptosis demonstrated increased rates of apoptosis in hepatocytes and biliary epithelial cells in PBC liver, and the rate of apoptosis in biliary epithelial cells was significantly reduced after treatment with ursodeoxycholic acid. Immunohistochemistry in PBC liver demonstrated significant reduction of fluorescence intensity for a 7H6 antigen in biliary epithelial cells, indicating the increased paracellular permeability of bile ducts, because cellular immunolocalization of that antigen has been shown to be inversely correlated with the paracellular permeability of the tight junction. These results suggest that, in biliary epithelial cells, retention of endotoxin, increased apoptosis, and increased permeability of tight junctions may be involved in the pathogenesis of PBC. ImagesFigure 1
DOI：
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发表时间：
1995-02
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
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作者：
R. Botla;J. Spivey;H. Aguilar;S. Bronk;G. Gores
通讯作者：
R. Botla;J. Spivey;H. Aguilar;S. Bronk;G. Gores
影响因子：
15.9
作者：
PATEL, T;BRONK, SF;GORES, GJ
通讯作者：
GORES, GJ