HEREDITARY CHRONIC CONJUGATED HYPERBILIRUBINEMIA IN MUTANT RATS CAUSED BY DEFECTIVE HEPATIC ANION TRANSPORT
HEREDITARY CHRONIC CONJUGATED HYPERBILIRUBINEMIA IN MUTANT RATS CAUSED BY DEFECTIVE HEPATIC ANION TRANSPORT
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DOI：
10.1002/hep.1840050408
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发表时间：
1985-01-01
期刊：
影响因子：
13.5
通讯作者：
LAMERS, WH
中科院分区：
文献类型：
--
作者：
JANSEN, PLM;PETERS, WH;LAMERS, WH
突变鼠株描述与常染色体隐性结合高胆红素血症。结合胆红素和四溴磺胺吡啶从肝脏到胆汁的转运严重受损，而从肝脏血浆中摄取有机阴离子是正常的。在生命的前10天，血清胆红素水平为147 +-。11 .mu。双偶联物占68.7%，单偶联物占27.9%。成年大鼠血清胆红素为33。8 .mu。Mol /l，双偶合物为81.8%，单偶合物为12.1%。0.1 .mu。正常成年大鼠未结合胆红素的Mol /l。胆汁酸代谢只受到轻微影响。在幼鼠中，血清胆汁酸水平是正常的。在成年大鼠中，胆汁酸水平升高到49。11 .mu。Mol /l比10 +-。6 .mu。Mol /l。突变大鼠的胆汁流量降至0.75%。50%。这可能是由于不依赖胆汁酸的胆汁部分减少所致。突变大鼠血清中肝脏标记酶活性正常。肝脏形态也正常。尿中共比例卟啉的总排泄量没有升高，但尿中共比例卟啉异构体I的排泄量增加，与人类杜宾-约翰逊综合征的模式相似。与杜宾-约翰逊综合征不同，突变大鼠没有典型的黑色肝色素。这些大鼠为研究胆汁形成和胆汁淤积机制提供了独特的模型。
A mutant rat strain is described with autosomal recessive conjugated hyperbilirubinemia. Transport of conjugated bilirubin and tetrabromosulfophthalein from liver to bile is severely impaired whereas uptake of organic anions from plasma of liver is normal. During the first 10 days of life, serum bilirubin levels are 147 .+-. 11 .mu.mol/l with 68.7% diconjugates and 27.9% monoconjugates. In adult rats, serum bilirubin is 33 .+-. 8 .mu.mol/l with 81.8% diconjugates and 12.1% monoconjugates vs. 0.3 .+-. 0.1 .mu.mol/l unconjugated bilirubin in normal adult rats. Bile acid metabolism is only mildly affected. In young rats, serum bile acid levels are normal. In adult rats, bile acid levels are elevated to 49 .+-. 11 .mu.mol/l vs. 10 .+-. 6 .mu.mol/l in normal rats. The bile flow in mutant rats is reduced to .apprx. 50%. This might be caused by a reduction of the bile acid-independent bile fraction. Liver marker enzyme activities in mutant rat serum are normal. Liver morphology is also normal. Total urinary coproporphyrin excretion is not elevated but urinary coproporphyrin isomer I excretion is increased, a pattern like that in Dubin-Johnson syndrome in humans. Unlike Dubin-Johnson syndrome, the mutant rats did not have the characteristic black hepatic pigment. These rats provide a unique model to study mechanisms of bile formation and cholestasis.