Zimmermann H, Reichen J, Zimmermann A, Sägesser H, Thenisch B, Höflin F
Department of Clinical Pharmacology, University of Bern, Switzerland.
Gastroenterology. 1992 Aug;103(2):579-89. doi: 10.1016/0016-5085(92)90850-x.
Biliary cirrhosis with portal hypertension and hepatocellular failure is a well-known complication of extrahepatic obstruction. It is unclear to what extent these changes are reversible by biliodigestive anastomosis. Therefore a rat model of relief of biliary obstruction was developed by performing Roux-en-Y choledochojejunostomy in rats after bile duct obstruction. Patency of the biliodigestive anastomosis was documented by biliary scintigraphy. Microsomal function was assessed in vivo by the aminopyrine breath test and portal hypertension by spleen pulp pressure. Microsomal function was markedly impaired in obstructed animals but recovered after biliodigestive anastomosis. Microsomal cytochrome P450 content paralleled these changes. Similarly, portal hypertension was reversed after successful relief of obstruction. Stereologic analysis showed that biliodigestive anastomosis partially reversed bile ductular proliferation and fibrosis. Studying the time course of recovery showed that restoration of microsomal function was achieved after 2 weeks whereas recovery from portal hypertension required 4 weeks of biliary drainage. Recovery of microsomal function was paralleled by normalization of microsomal lipid composition while resolution of portal hypertension occurred parallel to resolution of the histologic abnormalities.
伴有门静脉高压和肝细胞衰竭的胆汁性肝硬化是肝外梗阻的一种众所周知的并发症。目前尚不清楚通过胆肠吻合术这些改变在多大程度上是可逆的。因此，在胆管梗阻后的大鼠中通过施行Roux-en-Y胆总管空肠吻合术建立了一个解除胆管梗阻的大鼠模型。通过胆道闪烁显像记录胆肠吻合口的通畅情况。通过氨基比林呼气试验在体内评估微粒体功能，并通过脾髓压评估门静脉高压。在梗阻动物中微粒体功能明显受损，但在胆肠吻合术后恢复。微粒体细胞色素P450含量与这些变化平行。同样，梗阻成功解除后门静脉高压得到逆转。体视学分析表明，胆肠吻合术部分逆转了胆管增生和纤维化。对恢复时间进程的研究表明，微粒体功能在2周后恢复，而从门静脉高压恢复则需要4周的胆汁引流。微粒体功能的恢复与微粒体脂质组成的正常化平行，而门静脉高压的消退与组织学异常的消退同时发生。
