Wannagat R J, Adler R D, Ockner R K
J Clin Invest. 1978 Feb;61(2):297-307. doi: 10.1172/JCI108939.
Previous studies showed that in rats with obstruction of the bile ducts draining the median and left hepatic lobes, and in rats with normal bile ducts in which the bile acid pool size and secretion were augmented by 48-h intraduodenal infusion of taurocholate, bile acid flux through secreting hepatocytes was increased. Under these conditions, taurocholate transport maximum exhibited a time-dependent adaptation to increased secretory load.Unexpectedly, bile acid-independent canalicular flow in these experimental models also was found to be increased when measured at 48 h. Relative to controls, bile acid-independent flow per gram of nonobstructed liver was increased approximately threefold in selectively obstructed rats and 43% in bile acid-loaded rats with normal ducts. In rats infused with bile acids at similar rates for only 16 h, no increase was observed. Studies with [(14)C]erythritol suggested that the increased bile flow under these conditions was of canalicular origin.NaK-ATPase activity in canaliculi-enriched liver plasma membrane preparations from the nonobstructed lobes of selectively obstructed rats and from 48-h bile acid-loaded rats was increased by 47% and 52%, respectively, relative to controls, but was not increased in membranes from 16-h bile acid-loaded rats. Canalicular membrane 5'-nucleotidase and Mg ATPase also were increased. These studies show that augmented bile acid flux through secreting liver causes an adaptive increase in bile acid-"independent" flow and in the activity of canalicular membrane enzymes. The mechanism by which bile acids modulate this and previously reported aspects of bile secretion remains to be elucidated.
先前的研究表明，在引流肝中叶和左叶的胆管梗阻的大鼠中，以及在胆管正常但通过十二指肠内输注牛磺胆酸盐48小时使胆汁酸池大小和分泌增加的大鼠中，通过分泌肝细胞的胆汁酸通量增加。在这些条件下，牛磺胆酸盐的最大转运量表现出对增加的分泌负荷的时间依赖性适应。出乎意料的是，在48小时测量时，这些实验模型中不依赖胆汁酸的胆小管流量也被发现增加。相对于对照组，在选择性梗阻的大鼠中，每克未梗阻肝脏的不依赖胆汁酸的流量增加了约三倍，在胆管正常但胆汁酸负荷的大鼠中增加了43%。在以相似速率仅输注胆汁酸16小时的大鼠中，未观察到增加。用[¹⁴C]赤藓糖醇进行的研究表明，在这些条件下增加的胆汁流量起源于胆小管。相对于对照组，来自选择性梗阻大鼠未梗阻叶的富含胆小管的肝质膜制剂以及来自48小时胆汁酸负荷大鼠的NaK-ATP酶活性分别增加了47%和52%，但在16小时胆汁酸负荷大鼠的质膜中未增加。胆小管膜5'-核苷酸酶和Mg ATP酶也增加。这些研究表明，通过分泌肝脏的胆汁酸通量增加会导致胆汁酸“非依赖性”流量以及胆小管膜酶活性的适应性增加。胆汁酸调节这一过程以及先前报道的胆汁分泌方面的机制仍有待阐明。
