Kuipers F, Dijkstra T, Havinga R, van Asselt W, Vonk R J
Biochem Pharmacol. 1985 May 15;34(10):1731-6. doi: 10.1016/0006-2952(85)90642-2.
Male Wistar rats were equipped with permanent catheters in the bile duct and the duodenum under ether anaesthesia, at least seven days before the experiments. By this technique, the enterohepatic circulation can be interrupted for bile collection without direct surgical intervention. 14C-Pentobarbital (26.6 mumole/100 g body wt) was injected intraperitoneally immediately before interruption of the enterohepatic circulation (NBD, Non-Bile Diverted) or after eight days of bile diversion (BD, Bile Diverted). In NBD rats, bile flow and biliary bile acid excretion were significantly reduced during the first hour after pentobarbital administration when compared to unanaesthetized controls, but markedly increased thereafter. Pentobarbital treatment slightly decreased biliary bile acid excretion in BD rats, but caused a 60% increase in bile flow. Within four hours 22.3 +/- 0.4% and 26.0 +/- 2.7% of the injected radioactivity was excreted into bile in NBD and BD rats, respectively. The calculated osmotic activity of pentobarbital and its metabolites was 47.8 +/- 5.2 microliter/mumole in NBD rats and 37.8 +/- 1.3 microliter/mumole in BD rats. Consequently, pentobarbital treatment affected the bile acid independent fraction of bile flow (BAIF). The calculated BAIF was 2.68 microliter/min/100 g body wt in unanaesthetized animals, but 4.27 microliter/min/100 g body wt in pentobarbital treated NBD rats. Corresponding values for BD rats were 1.70 and 2.38 microliter/min/100 g body wt. It is concluded that pentobarbital anaesthesia affects bile production in the rat by direct and indirect means. Firstly, pentobarbital and its metabolites are rapidly excreted into bile and exert a significant choleretic effect, thereby increasing the BAIF. Secondly, pentobarbital anaesthesia retards the exhaustion of the intestinal bile acid pool, which leads to secondary changes in the biliary excretion process.
在实验前至少七天,将雄性Wistar大鼠在乙醚麻醉下于胆管和十二指肠植入永久性导管。通过这种技术,无需直接手术干预即可中断肠肝循环以收集胆汁。在中断肠肝循环前即刻(NBD,非胆汁转流组)或胆汁转流八天后(BD,胆汁转流组),经腹腔注射14C-戊巴比妥(26.6微摩尔/100克体重)。与未麻醉的对照组相比,在戊巴比妥给药后的第一小时内,NBD组大鼠的胆汁流量和胆汁中胆汁酸排泄显著减少,但此后显著增加。戊巴比妥处理使BD组大鼠的胆汁中胆汁酸排泄略有减少,但胆汁流量增加了60%。在四小时内,NBD组和BD组大鼠分别有22.3±0.4%和26.0±2.7%的注入放射性物质排泄到胆汁中。戊巴比妥及其代谢产物在NBD组大鼠中的计算渗透活性为47.8±5.2微升/微摩尔,在BD组大鼠中为37.8±1.3微升/微摩尔。因此,戊巴比妥处理影响了胆汁流量中不依赖胆汁酸的部分(BAIF)。在未麻醉动物中计算出的BAIF为2.68微升/分钟/100克体重,但在戊巴比妥处理的NBD组大鼠中为4.27微升/分钟/100克体重。BD组大鼠的相应值分别为1.70和2.38微升/分钟/100克体重。结论是戊巴比妥麻醉通过直接和间接方式影响大鼠胆汁生成。首先,戊巴比妥及其代谢产物迅速排泄到胆汁中并发挥显著的利胆作用,从而增加BAIF。其次,戊巴比妥麻醉延缓了肠道胆汁酸池的耗尽,这导致胆汁排泄过程的继发性变化。