Effect of endotoxin on bile acid transport in rat liver: a potential model for sepsis-associated cholestasis.
Effect of endotoxin on bile acid transport in rat liver: a potential model for sepsis-associated cholestasis.
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DOI：
10.1152/ajpgi.1996.271.1.g137
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发表时间：
1996-07
期刊：
影响因子：
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通讯作者：
R. Moseley;Wei Wang;Hiroaki Takeda;K. Lown;Lawton Shick;M. Ananthanarayanan;F. Suchy
中科院分区：
文献类型：
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作者：
R. Moseley;Wei Wang;Hiroaki Takeda;K. Lown;Lawton Shick;M. Ananthanarayanan;F. Suchy
肝内胆汁淤积可归因于内毒素和肿瘤坏死因子-α等细胞因子对胆汁酸转运的影响。为探讨脓毒症相关胆汁淤积的机制，本实验观察了对照组和内毒素[LPS]处理的大鼠肝基底外侧(BLPM)和肝小管(CLPM)质膜微囊以及经TNF-α处理后形成的质膜微囊的牛磺胆酸盐转运。脂多糖处理后，bLPM和cLPM囊泡对Na(+)依赖的[3 H]牛磺胆酸摄取减少，膜电位依赖和ATP依赖的[3 H]牛磺胆酸转运减少。在经肿瘤坏死因子-α处理的动物的膜小泡中，钠(+)依赖的[~3H]牛磺胆酸摄取也减少。Northern印迹杂交显示，在内毒素和肿瘤坏死因子-α处理后，胆汁酸转运体(Ntcp)和小管外膜三磷酸腺苷酶的基因表达水平降低。对脂多糖处理的动物的膜提取物的免疫印迹分析显示，这些假定的胆汁酸转运体的水平降低。这些炎症反应介质和其他炎症反应介质在肝窦和小管膜区的胆汁酸转运受损可能是脓毒症相关性胆汁淤积的原因。
Intrahepatic cholestasis in the setting of extrahepatic bacterial infection has been attributed to the effects of endotoxin and cytokines such as tumor necrosis factor-alpha (TNF-alpha) on bile acid transport. To define the mechanism of sepsis-associated cholestasis, taurocholate transport was examined in basolateral (bLPM) and canalicular (cLPM) rat liver plasma membrane vesicles derived from control and endotoxin [lipopolysaccharide (LPS)]-treated animals and in plasma membrane vesicles prepared after TNF-alpha treatment. Na(+)-dependent [3H]taurocholate uptake and both membrane-potential-dependent and ATP-dependent [3H]taurocholate transport were reduced in bLPM and cLPM vesicles, respectively, after LPS treatment. In membrane vesicles from TNF-alpha-treated animals, Na(+)-dependent [3H]taurocholate uptake was also reduced. Northern blot hybridization, using cDNA probes for the putative sinusoidal bile acid transporter (Ntcp) and canalicular ecto-adenosinetriphosphatase, demonstrated decreased mRNA levels after LPS and TNF-alpha treatment. Immunoblot analysis of membrane extracts from LPS-treated animals revealed decreased levels of these putative bile acid transporters. Impaired bile acid transport at the sinusoidal and canalicular membrane domains by these and other mediators of the inflammatory response may account for sepsis-associated cholestasis.