Okuda H, Sorrentino D, Alpini G, Tavoloni N, Jones M J, Kiang C L, Berk P D
Polly Annenberg Levee Hematology Center, New York, New York.
Proc Soc Exp Biol Med. 1988 Feb;187(2):202-8. doi: 10.3181/00379727-187-42655.
An increase in bile flow after phenobarbital administration occurs in the rat and other species; however, the mechanism(s) of the choleretic effect is incompletely understood and the role of the increase in liver weight is controversial. We therefore measured bile flow, bile acid secretion and pool size in male Sprague-Dawley rats pretreated with phenobarbital (75 mg/kg/day) for 6 days; liver weight, liver cell volume and DNA content were also evaluated. Phenobarbital treatment increased liver weight and mean hepatocyte volume by 39 and 26%, respectively, while total DNA content did not change, thus indicating that the hepatomegaly results principally from hypertrophy rather than hyperplasia. Bile flow was significantly higher in treated rats when expressed per unit of body weight (64.6 +/- 2.4 (S.E.) vs 53.3 +/- 1.6 microliter/min/kg; P less than 0.05) but was unchanged when expressed per gram of liver (1.40 +/- 0.04 vs 1.37 +/- 0.06 microliter/min/g; P greater than 0.5). The initial bile acid secretion rate and pool size were both significantly reduced in the phenobarbital group compared to controls (1224.2 +/- 110.4 vs 1656.6 +/- 163.2 nmol/kg/min and 562.8 +/- 41.5 vs 814.3 +/- 78.3 mumol/kg; both P less than 0.05), whereas the basal synthetic rate was unchanged. These findings suggest that the enlarged, phenobarbital-treated hepatocyte produces more bile than the normal cell, despite the decreased secretion of bile acids. Therefore, the drug-induced choleresis involves a selective increase in the bile acid-independent fraction of bile flow.
给予苯巴比妥后，大鼠及其他物种的胆汁流量会增加；然而，利胆作用的机制尚未完全明确，肝脏重量增加所起的作用也存在争议。因此，我们对雄性斯普拉格-道利大鼠进行了研究，这些大鼠预先接受苯巴比妥（75毫克/千克/天）处理6天，随后测量其胆汁流量、胆汁酸分泌及胆汁酸池大小；同时还评估了肝脏重量、肝细胞体积及DNA含量。苯巴比妥处理使肝脏重量和平均肝细胞体积分别增加了39%和26%，而总DNA含量未发生变化，这表明肝肿大主要是由细胞肥大而非细胞增生所致。以每单位体重计算时，处理组大鼠的胆汁流量显著更高（64.6±2.4（标准误）对53.3±1.6微升/分钟/千克；P<0.05），但以每克肝脏计算时则无变化（1.40±0.04对1.37±0.06微升/分钟/克；P>0.5）。与对照组相比，苯巴比妥组的初始胆汁酸分泌率和胆汁酸池大小均显著降低（1224.2±110.4对1656.6±163.2纳摩尔/千克/分钟以及562.8±41.5对814.3±78.3微摩尔/千克；两者P均<0.05），而基础合成率未变。这些发现表明，尽管胆汁酸分泌减少，但经苯巴比妥处理后肿大的肝细胞比正常细胞产生的胆汁更多。因此，药物诱导的利胆作用涉及胆汁流量中不依赖胆汁酸部分的选择性增加。
