Kotal P, Van der Veere C N, Sinaasappel M, Elferink R O, Vítek L, Brodanová M, Jansen P L, Fevery J
Charles University, 1st Medical Faculty, Prague, Czech Republic.
Pediatr Res. 1997 Aug;42(2):195-200. doi: 10.1203/00006450-199708000-00011.
Patients with Crigler-Najjar syndrome and Gunn rats cannot form bilirubin glucuronides owing to a lack of bilirubin UDP-glucuronosyltransferase activity. Because increased serum and tissue bilirubin levels remain constant, an alternative excretory route has to substitute for this deficiency. Gunn rats excrete in bile only 2-13% of the bilirubins eliminated in Wistar rats. In contrast, the biliary excretion rate of urobilinogen in Gunn and Wistar rats is comparable. The sum of bilirubins and urobilinogen excreted in the bile of Gunn rats amounts to 10-30% of pigments excreted in Wistar rats. Despite this low biliary excretion, the intestinal content and fecal excretion of bile pigments in Gunn and Wistar rats were similar. These data support an extrabiliary entrance of unconjugated bilirubin into the intestine. Additional proof for this was found in that the intestinal lumen of Gunn rats still contains a high amount of bilirubins and urobilinogen after 3 d of external biliary drainage. A similar procedure in Wistar rats resulted in the complete disappearance of bile pigments from the intestine. The direct transmural transport of bilirubin from blood to all parts of the intestinal lumen was demonstrated by injecting 14C-bilirubin i.v. into Gunn rats with isolated parts of small and large intestine. In Crigler-Najjar and Gilbert's syndrome patients, the biliary excretion of bile pigments has previously been shown to be strongly reduced. Their stools, however, contained approximately the same amount of bile pigments as in normal subjects. Although only traces of unconjugated bilirubin were detected in the stool of normal persons (4 +/- 3% of total bile pigments), higher amounts were found in patients with Crigler-Najjar disease (20 +/- 12&). These results suggest a direct intestinal permeation of unconjugated bilirubin in severe unconjugated hyperbilirubinemia both in man and rats.
患有克里格勒 - 纳贾尔综合征的患者和冈恩大鼠由于缺乏胆红素UDP - 葡萄糖醛酸基转移酶活性而无法形成胆红素葡萄糖醛酸酯。由于血清和组织胆红素水平升高保持恒定，必须有替代排泄途径来弥补这一缺陷。冈恩大鼠胆汁中排泄的胆红素仅占Wistar大鼠消除胆红素的2 - 13%。相比之下，冈恩大鼠和Wistar大鼠中尿胆原的胆汁排泄率相当。冈恩大鼠胆汁中排泄的胆红素和尿胆原总量占Wistar大鼠排泄色素的10 - 30%。尽管胆汁排泄量低，但冈恩大鼠和Wistar大鼠胆汁色素的肠道含量和粪便排泄量相似。这些数据支持未结合胆红素经胆管外途径进入肠道。这一点的额外证据是，在冈恩大鼠进行3天的外部胆管引流后，其肠腔中仍含有大量胆红素和尿胆原。在Wistar大鼠中进行类似操作会导致胆汁色素从肠道中完全消失。通过将14C - 胆红素静脉注射到具有分离的小肠和大肠部分的冈恩大鼠中，证明了胆红素从血液到肠腔各部位的直接跨壁转运。先前已表明，在克里格勒 - 纳贾尔综合征和吉尔伯特综合征患者中，胆汁色素的胆汁排泄显著减少。然而，他们的粪便中胆汁色素含量与正常受试者大致相同。尽管在正常人粪便中仅检测到微量未结合胆红素（占总胆汁色素的4±3%），但在克里格勒 - 纳贾尔病患者中发现的量更高（20±12%）。这些结果表明，在人和大鼠的严重未结合型高胆红素血症中，未结合胆红素可直接透过肠道。
