Hatoff D E, Katz R F, Ringard A A
Proc Soc Exp Biol Med. 1983 Jun;173(2):227-30. doi: 10.3181/00379727-173-41636.
We studied the induction of hepatic alkaline phosphatase by colchicine, a drug which impairs bile flow. By analogy to bile duct obstruction, where retained bile acids induce alkaline phosphatase, we hypothesized that the mechanism of induction involves the drug's cholestatic property and subsequent intrahepatic retention of bile acids. After administering colchicine to bile-fistula rats, we monitored bile flow. In colchicine-treated rats which did not develop cholestasis, we varied the transhepatic flux of taurocholate 15-fold over the physiologic range in order to study the role of intrahepatic bile acids. Induction of alkaline phosphatase was observed when cholestasis was absent and the bile acid flux was 5% of normal. The magnitude of enzyme induction was not augmented by increasing the transhepatic flux of taurocholate. The results demonstrate that colchicine induces hepatic alkaline phosphatase by a mechanism which operates independently of cholestasis and is not modified by the level of bile acid in the liver.
我们研究了秋水仙碱对肝碱性磷酸酶的诱导作用，秋水仙碱是一种会损害胆汁流动的药物。类比胆管阻塞（在胆管阻塞时，潴留的胆汁酸会诱导碱性磷酸酶产生），我们推测诱导机制涉及该药物的胆汁淤积特性以及随后肝内胆汁酸的潴留。给胆瘘大鼠施用秋水仙碱后，我们监测了胆汁流动情况。在未发生胆汁淤积的秋水仙碱处理大鼠中，我们在生理范围内将牛磺胆酸盐的经肝通量改变了15倍，以研究肝内胆汁酸的作用。当不存在胆汁淤积且胆汁酸通量为正常水平的5%时，观察到了碱性磷酸酶的诱导。增加牛磺胆酸盐的经肝通量并没有增强酶诱导的程度。结果表明，秋水仙碱通过一种独立于胆汁淤积起作用且不受肝脏中胆汁酸水平影响的机制来诱导肝碱性磷酸酶。
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