Kuipers F, Havinga R, Bosschieter H, Toorop G P, Hindriks F R, Vonk R J
Gastroenterology. 1985 Feb;88(2):403-11. doi: 10.1016/0016-5085(85)90499-8.
Several compounds, in particular bile acids, undergo enterohepatic circulation (EHC). Limited data are available on the pathophysiologic aspects of this circulation. In the present study we describe a surgical technique in rats that allows a long-term, reversible interruption of the EHC and monitoring of peripheral blood levels without direct surgical intervention. This technique excludes the effects of anesthesia and surgical trauma. The model's validity has been tested extensively. We used this animal model to investigate acute and chronic effects of interruption and subsequent restoration of the EHC on (a) nutritional status, (b) plasma cholesterol levels and hepatic cholesterol synthesis, and (c) biliary bile acid, phospholipid, and cholesterol excretion. Interruption of the EHC resulted in an increased food intake and enhanced fecal energy loss, caused by a less efficient intestinal absorption. Plasma cholesterol concentrations declined immediately after the interruption of the EHC, but returned to almost control values during bile diversion. A marked overshoot followed the subsequent restoration of the EHC. Hepatic cholesterol synthesis showed a five-fold increase after 8 days of bile diversion but returned to control values within 2 days after restoration of the EHC. After interruption of the EHC, bile acid, phospholipid, and cholesterol excretion decreased sharply but stabilized after 3 h at 7.6%, 20%, and 23%, respectively, of their initial values. Bile acid output, representing hepatic synthesis, slowly increased over 4 days, but never exceeded 13% of its value during intact EHC. Subsequent restoration of the EHC could rapidly reverse the observed effects of the interruption. The animal model described in the present study is an excellent tool in studying the acute and chronic effects of disturbances of the EHC.
几种化合物，特别是胆汁酸，会经历肠肝循环（EHC）。关于这种循环的病理生理方面的数据有限。在本研究中，我们描述了一种大鼠手术技术，该技术可长期、可逆地中断肠肝循环，并在无需直接手术干预的情况下监测外周血水平。该技术排除了麻醉和手术创伤的影响。该模型的有效性已得到广泛测试。我们使用这个动物模型来研究肠肝循环中断及随后恢复对以下方面的急性和慢性影响：（a）营养状况，（b）血浆胆固醇水平和肝脏胆固醇合成，以及（c）胆汁中胆汁酸、磷脂和胆固醇的排泄。肠肝循环中断导致食物摄入量增加和粪便能量损失增加，这是由于肠道吸收效率降低所致。肠肝循环中断后，血浆胆固醇浓度立即下降，但在胆汁引流期间恢复到几乎与对照值相同的水平。肠肝循环随后恢复后出现明显的超调。胆汁引流8天后，肝脏胆固醇合成增加了五倍，但在肠肝循环恢复后2天内恢复到对照值。肠肝循环中断后，胆汁酸、磷脂和胆固醇的排泄急剧下降，但在3小时后分别稳定在其初始值的7.6%、20%和23%。代表肝脏合成的胆汁酸输出在4天内缓慢增加，但从未超过完整肠肝循环期间其值的13%。随后肠肝循环的恢复可迅速逆转观察到的中断效应。本研究中描述的动物模型是研究肠肝循环紊乱的急性和慢性影响的优秀工具。
