Transport of chenodeoxycholic acid and its 3-alpha- and 7-alpha-sulfates by isolated perfused rat liver.
Transport of chenodeoxycholic acid and its 3-alpha- and 7-alpha-sulfates by isolated perfused rat liver.
复制标题
鹅去氧胆酸及其 3-α- 和 7-α-硫酸盐通过离体灌注大鼠肝脏的转运。
DOI：
10.1002/hep.1840120419
复制
发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Wolkoff,AW
中科院分区：
文献类型：
--
作者：
Gärtner,U;Goeser,T;Stiehl,A;Raedsch,R;Wolkoff,AW
在胆汁淤积患者中，硫酸化胆汁酸水平升高。鹅去氧胆酸的硫酸酯是这些胆汁酸硫酸盐中最丰富的。这些化合物被肝脏吸收并排泄到胆汁中，尽管与未硫酸化的胆汁酸相比，它们的血浆清除率和胆汁排泄率降低。尚不清楚这是否是由于内源性肝脏摄取或胆汁排泄的差异。在本研究中，鹅去氧胆酸3-α-硫酸盐，鹅去氧胆酸7-α-硫酸盐和未硫酸化的鹅去氧胆酸在离体灌注大鼠肝脏中的单程转运动力学进行了定量。7-α-和3-α-硫酸化衍生物的流入量分别为鹅去氧胆酸的57%和20%。这三种化合物与白蛋白的结合同样良好，表明这不是其差异摄取的一个因素。虽然这些化合物的单程提取不同，但肝脏吸收的材料的胆汁排泄是相同的。无论检测哪种胆汁酸硫酸盐，胆汁流量或胆汁排泄率均无差异。这些结果表明，先前由其他人观察到的硫酸化胆汁酸的低血浆消除可以通过低肝内流来解释。硫酸化导致的肝脏转运减少可能导致肾脏对胆汁酸的消除增强。（Hepatology 1990; 12：738-742）。
In patients with cholestasis, levels of sulfated bile acids rise. Sulfate esters of chenodeoxycholic acid are the most abundant of these bile acid sulfates. These compounds are taken up by the liver and excreted into bile, although their plasma clearance and biliary excretion are reduced compared with that of unsulfated bile acids. It is not clear whether this is due to differences in intrinsic hepatic uptake or biliary excretion. In the present study, single-pass transport kinetics of chenodeoxycholic acid 3-α-sulfate, chenodeoxycholic acid 7-α-sulfate and unsulfated chenodeoxycholic acid were quantified in isolated perfused rat liver. Influx of the 7-α-and 3-α-sulfated derivatives was 57% and 20% that of chenodeoxycholic acid, respectively. These three compounds bound to albumin equally well, indicating that this was not a factor in their differential uptake. Although single-pass extraction of each of these compounds differed, biliary excretion of material taken up by the liver was identical. There was no difference in bile flow or biliary excretion rate, regardless of which bile acid sulfate was tested. These results indicate that the low plasma elimination of sulfated bile acids previously observed by others can be explained by low hepatic influx. The diminished transport into liver resulting from sulfation could lead to enhanced elimination of bile acids by the kidney.(HEPATOLOGY 1990; 12: 738-742).