Scheibner J, Fuchs M, Schiemann M, Tauber G, Hörmann E, Stange E F
Department of Internal Medicine, Medical University of Ulm, Germany.
Hepatology. 1993 Jun;17(6):1095-102.
The present study defines the origin of cholesterol subserving bile acid synthesis in male rats with an extracorporal bile duct by labeling newly formed cholesterol with tritiated water. Within 6 hr after interruption of the enterohepatic circulation, the bile acid pool was depleted. At this early time point the proportion from de novo cholesterol was 8% and 12% for biliary cholesterol and cholate, but 18% and 19% for muricholate and chenodeoxycholate, respectively. This proportion gradually rose to 40%, 34%, 51% and 51%, respectively, at 15 to 30 hr. At 78 hr after bile diversion, 64% of cholate was labeled, compared with 84% to 88% of the other biliary lipids and 71% of plasma cholesterol. Total and labeled bile acid secretion exhibited the same diurnal rhythm. To allow differentiation between direct hepatocytic de novo synthesis of bile acids from acetate and recycling of labeled plasma cholesterol, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (pravastatin) was infused from 54 to 78 hr. It suppressed total synthesis of primary bile acids by 60% to 80% but decreased the tritium label of bile acids only from a range of 74% to 92% (54 hr) to a range of 54% to 63% (78 hr), which was in the range of plasma cholesterol (58%). We conclude that bile acids and biliary cholesterol are synthesized mostly from preformed (i.e., plasma) cholesterol, both immediately after depletion of the pool in enterohepatic circulation and after derepression. Moreover, the hepatic cholesterol pools subserving the synthesis of different bile acids and biliary cholesterol secretion are not identical.
本研究通过用氚水标记新形成的胆固醇，确定了体外胆管雄性大鼠中用于胆汁酸合成的胆固醇来源。在肠肝循环中断后6小时内，胆汁酸池被耗尽。在此早期时间点，从头合成胆固醇在胆汁胆固醇和胆酸盐中的比例分别为8%和12%，但在鼠胆酸盐和鹅去氧胆酸盐中分别为18%和19%。该比例在15至30小时时分别逐渐升至40%、34%、51%和51%。在胆汁引流78小时后，64%的胆酸盐被标记，相比之下，其他胆汁脂质的标记率为84%至88%，血浆胆固醇的标记率为71%。总胆汁酸分泌和标记胆汁酸分泌表现出相同的昼夜节律。为了区分从乙酸盐直接进行肝细胞从头合成胆汁酸和标记血浆胆固醇的再循环，在54至78小时内注入3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂（普伐他汀）。它将初级胆汁酸的总合成抑制了60%至80%，但仅将胆汁酸的氚标记从74%至92%（54小时）的范围降低至54%至63%（78小时）的范围，该范围与血浆胆固醇（58%）的范围相同。我们得出结论，在肠肝循环池中耗尽后以及解除抑制后，胆汁酸和胆汁胆固醇大多由预先形成的（即血浆）胆固醇合成。此外，用于合成不同胆汁酸和胆汁胆固醇分泌的肝脏胆固醇池并不相同。
