CORRECTION OF CONGENITAL INDIRECT HYPERBILIRUBINEMIA BY SMALL-INTESTINAL TRANSPLANTATION
CORRECTION OF CONGENITAL INDIRECT HYPERBILIRUBINEMIA BY SMALL-INTESTINAL TRANSPLANTATION
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DOI：
10.1016/s0002-9610(99)80105-6
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发表时间：
1995-01-01
影响因子：
3
通讯作者：
JAFFE, BM
中科院分区：
文献类型：
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作者：
MEDLEY, MM;HOOKER, RL;JAFFE, BM
简介：Crigler-Najjar综合征，I型，是一种以肝胆红素糖醛酸化完全缺失为特征的疾病。先天性间接高胆红素血症是由于常染色体隐性缺乏酶，尿苷二磷酸葡萄糖醛基转移酶（UDPGT）。近交纯合子Gunn大鼠也缺乏UDPGT，表现为未结合的高胆红素血症，是Crigler-Najjar综合征的优秀动物模型。本研究旨在测试正常Wistar大鼠供体肠移植对肝脏胆红素结合不足的纠正能力。材料和方法：在第一阶段，Gunn大鼠在Wistar大鼠（实验）或Gunn大鼠（对照）前接受40厘米异位小肠移植。在第2阶段，15- 20厘米Wistar-to-Gunn空肠移植物被放置在异位或正位（肠连续性）。大鼠给予环孢素A (CsA) 5 mg/kg / d。移植后每隔一周分光光度法测定血清胆红素水平。在第二阶段，使用已知数量的胆红素作为底物，在0、2、4和8周时定量UDPGT活性。结果：40cm异位移植大鼠总胆红素水平明显降低。从初始值7.12 +/- 0.59 mg/dL，水平达到最低点4.23 +/- 0.27 mg/dL。血清间接胆红素水平同时下降（5.04 +/- 0.54 mg/dL至2.74 +/- 0.23 mg/dL）。6周后，胆红素水平开始向移植前水平上升。相比之下，对照组大鼠的胆红素水平没有显著变化，15至20厘米异位Wistar-to-Gunn移植引起的总胆红素水平和间接胆红素水平的下降在质量上相似。原位（连续）Wistar-to-Gunn移植更快地降低了血清胆红素水平，并且在整个8周的研究期间效果持续。移植后1周，总胆红素水平从5.11 +/- 0.48 mg/dL降至2.41 +/- 0.16 mg/dL (P
INTRODUCTION: Crigler-Najjar syndrome, type I, is a disease characterized by complete absence of hepatic bilirubin glucuronidation. The congenital indirect hyperbilirubinemia is due to an autosomal recessive deficiency of the enzyme, uridine diphosphate glucuronosyl transferase (UDPGT). The inbred homozygous Gunn rat is also deficient in UDPGT, exhibits unconjugated hyperbilirubinemia, and is an excellent animal model of the Crigler-Najjar syndrome. This study was performed to test the ability of transplanted intestine from normal Wistar rat donors to correct the deficiency in hepatic bilirubin conjugation.MATERIALS AND METHODS: In phase 1, Gunn rats underwent 40-cm heterotopic small-bowel transplants front either Wistar (experimental) or Gunn (control) rats. In phase 2, 15- to 20-cm Wistar-to-Gunn jejunal transplants were placed either heterotopically or orthotopically (in intestinal continuity). Ah rats were treated with cyclosporin A (CsA), 5 mg/kg per day. Serum bilirubin levels were determined spectrophotometrically at weekly intervals posttransplantation. In phase 2, UDPGT activity was quantitated at 0, 2, 4, and 8 weeks using known quantities of bilirubin as substrate.RESULTS: Total bilirubin levels decreased significantly in the 40-cm heterotopic transplant recipient rats. From the initial values of 7.12 +/- 0.59 mg/dL, levels reached the nadir of 4.23 +/- 0.27 mg/dL. A parallel drop in serum levels of indirect bilirubin was noted (5.04 +/- 0.54 mg/dL to 2.74 +/- 0.23 mg/dL). After 6 weeks, bilirubin levels began to rise toward pretransplant values. In contrast, there was no significant change in bilirubin levels in the control Gunn-to-Gunn rats,Fifteen- to 20-cm heterotopic Wistar-to-Gunn transplants caused a qualitatively similar drop in total and indirect bilirubin levels. Orthotopic (in continuity) Wistar-to-Gunn transplants lowered serum bilirubin levels more rapidly, and the effect was sustained throughout the 8-week study period. By 1 week posttransplantation, total bilirubin levels dropped from 5.11 +/- 0.48 mg/dL to 2.41 +/- 0.16 mg/dL (P