Ursodeoxycholic acid aggravates bile infarcts in bile duct-ligated and Mdr2 knockout mice via disruption of cholangioles
Ursodeoxycholic acid aggravates bile infarcts in bile duct-ligated and Mdr2 knockout mice via disruption of cholangioles
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DOI：
10.1053/gast.2002.35948
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发表时间：
2002-10-01
期刊：
影响因子：
29.4
通讯作者：
Trauner, M
中科院分区：
文献类型：
--
作者：
Fickert, P;Zollner, G;Trauner, M
背景与目的：熊去氧胆酸（UDCA）在胆道梗阻中的作用尚不清楚。我们旨在确定UDCA在胆管结扎和Mdr 2基因敲除（Mdr 2（-/-））胆管狭窄小鼠中的作用。研究方法：喂食UDCA（0.5% wt/wt）或对照饲料的小鼠接受胆总管结扎（CBDL）、选择性胆管结扎（SBDL）或假手术。还向2月龄Mdr 2（-/-）小鼠饲喂UDCA。研究血清生化、肝组织学和死亡率。通过塑化、印度墨水注射和电子显微镜研究胆道。通过胆管测压法测定UDCA对胆汁压力的影响。结果如下：CBDL小鼠喂食UDCA增加了胆汁压力，随后胆管破裂和肝细胞坏死加重，导致死亡率显著增加。在SBDL小鼠中饲喂UDCA仅加重了结扎肝叶的肝损伤。Mdr 2（-/-）小鼠出现类似于硬化性胆管炎的肝脏病变，其特征是胆管狭窄和扩张。UDCA在这些动物中诱导胆汁梗死。结论：UDCA通过其利胆作用引起的胆汁压力升高导致胆管破裂，从而减轻胆道梗阻小鼠的胆汁梗死和肝细胞坏死。
Background & Aims: The effects of ursodeoxycholic acid (UDCA) in biliary obstruction are unclear. We aimed to determine the effects of UDCA in bile duct-ligated and in Mdr2 knockout (Mdr2(-/-)) mice with biliary strictures. Methods: Mice fed UDCA (0.5% wt/wt) or a control diet were subjected to common bile duct ligation (CBDL), selective bile duct ligation (SBDL), or sham operation. UDCA was also fed to 2-month-old Mdr2(-/-) mice. Serum biochemistry, liver histology, and mortality rates were investigated. The biliary tract was studied by plastination, India ink injection, and electron microscopy. The effects of UDCA on biliary pressure were determined by cholangiomanometry. Results: UDCA feeding in CBDL mice increased biliary pressure, with subsequent rupture of cholangioles and aggravation of hepatocyte necroses, resulting in significantly increased mortality. UDCA feeding in SBDL mice aggravated liver injury exclusively in the ligated lobe. Mdr2(-/-) mice developed liver lesions resembling sclerosing cholangitis characterized by biliary strictures and dilatations. UDCA induced bile infarcts, in these animals. Conclusions: UDCA aggravates bile infarcts and hepatocyte necroses in mice with biliary obstruction via disruption of cholangioles as a result of increased biliary pressure caused by its choleretic action.