Zimmermann H, Reichen J, Sägesser H, Tenisch B, Zimmermann A
Department of Clinical Pharmacology, University of Berne, Switzerland.
J Hepatol. 1993 Aug;19(1):110-6. doi: 10.1016/s0168-8278(05)80184-9.
In this study we investigated whether the retention of compounds which are excreted into the bile could contribute to portal hypertension in secondary biliary cirrhosis. Choledochovenous fistulas were grown in rats for 4 weeks. 6/13 of the animals had biochemical evidence of partial obstruction. Microsomal function, as measured by the aminopyrine breath test, was decreased in all animals with biliary retention while microsomal cytochrome P-450 content was decreased only in rats with evidence of obstruction. All animals with biliary retention with or without partial obstruction had portal hypertension. Animals with biliary retention and partial obstruction had hypercholeresis but decreased bile salt excretion. All animals with a chronic catheter in the biliary tree had a loss of the negative permselectivity of the sinusoidal-canalicular barrier and decreased maximal bile secretory pressure. Only animals with biochemical evidence of obstruction had moderate fibrosis and ductular proliferation as determined by stereological techniques. Unexpectedly, morphometric analysis also revealed an increase in hepatocyte mass induced by biliary retention. We conclude that bile contains a compound(s) which induces portal hypertension. This putative substance is neither bilirubin nor a bile acid since portal hypertension was also observed in animals with biliary retention without obstructive signs.
在本研究中，我们调查了排入胆汁的化合物的潴留是否会导致继发性胆汁性肝硬化中的门静脉高压。在大鼠中建立胆总管-静脉瘘4周。13只动物中有6只具有部分梗阻的生化证据。通过氨基比林呼吸试验测量的微粒体功能，在所有有胆汁潴留的动物中均降低，而微粒体细胞色素P-450含量仅在有梗阻证据的大鼠中降低。所有有胆汁潴留的动物，无论有无部分梗阻，均有门静脉高压。有胆汁潴留和部分梗阻的动物胆汁分泌过多，但胆盐排泄减少。所有在胆管树中留置慢性导管的动物，其窦状隙-胆小管屏障的负选择通透性丧失，最大胆汁分泌压力降低。通过体视学技术确定，只有有梗阻生化证据的动物有中度纤维化和小胆管增生。出乎意料的是，形态计量分析还显示胆汁潴留可诱导肝细胞质量增加。我们得出结论，胆汁中含有一种可诱导门静脉高压的化合物。这种假定的物质既不是胆红素也不是胆汁酸，因为在没有梗阻迹象的胆汁潴留动物中也观察到了门静脉高压。
