Muraca M, Fevery J, Blanckaert N
Gastroenterology. 1987 Feb;92(2):309-17. doi: 10.1016/0016-5085(87)90123-5.
The pattern of serum bilirubins was determined in serum of humans and rats with unconjugated hyperbilirubinemia due to increased pigment load or defective hepatic conjugation. Bilirubin ester conjugates were present in all serum samples tested and were identified as bilirubin 1-O-acyl glucuronides. In Gilbert's syndrome, the concentration of total conjugates was comparable to the values in healthy control subjects. Because the concentration of unconjugated pigment was increased, the fraction of conjugated relative to total bilirubins was markedly decreased. Sera from patients with Crigler-Najjar disease differed from those with Gilbert's syndrome by the higher unconjugated bilirubin levels and the undetectability of diconjugated bilirubins. A striking finding was that in hemolytic disease, the concentration of both monoconjugates and diconjugates was enhanced in parallel with the increase of unconjugated pigment. Therefore, the fraction of conjugated relative to total bilirubins remained within the normal range. As in Gilbert's syndrome, heterozygote R/APfd-j/+ rats with impaired hepatic bilirubin conjugation exhibit an increased unconjugated bilirubin level in serum, whereas the concentration of total conjugates was comparable to the values in normal rats. In serum of normal rats loaded intraperitoneally with unconjugated bilirubin, both unconjugated and mono- and diconjugated bilirubins were increased in parallel so that the ratio of unconjugated to esterified pigment remained unaffected. Decreased hepatic conjugation or increased bilirubin load was associated with a lower percentage of diconjugates relative to total conjugates both in human and rat serum. The present results are consistent with a compartmental model in which there is bidirectional transfer across the sinusoidal membrane for unconjugated bilirubin as well as for the bilirubin glucuronides. Because typical patterns of serum bilirubins are found in Gilbert's syndrome and patients with hemolytic hyperbilirubinemia, determination of esterified bilirubins in serum is of value to study the pathophysiology and the differential diagnosis of unconjugated hyperbilirubinemia.
对因色素负荷增加或肝脏结合功能缺陷而导致非结合性高胆红素血症的人类和大鼠血清中的血清胆红素模式进行了测定。在所有检测的血清样本中均存在胆红素酯结合物，并被鉴定为胆红素1-O-酰基葡萄糖醛酸酯。在吉尔伯特综合征中，总结合物的浓度与健康对照受试者的值相当。由于非结合色素的浓度增加，结合胆红素相对于总胆红素的比例显著降低。克里格勒-纳贾尔病患者的血清与吉尔伯特综合征患者的血清不同，前者非结合胆红素水平更高，且检测不到双结合胆红素。一个显著的发现是，在溶血性疾病中，单结合物和双结合物的浓度随着非结合色素的增加而平行升高。因此，结合胆红素相对于总胆红素的比例保持在正常范围内。与吉尔伯特综合征一样，肝脏胆红素结合功能受损的杂合子R/APfd-j/+大鼠血清中非结合胆红素水平升高，而总结合物的浓度与正常大鼠的值相当。在腹腔内注射非结合胆红素的正常大鼠血清中，非结合胆红素以及单结合和双结合胆红素均平行增加，因此非结合胆红素与酯化色素的比例不受影响。在人类和大鼠血清中，肝脏结合功能降低或胆红素负荷增加均与双结合物相对于总结合物的比例降低有关。目前的结果与一个区室模型一致，在该模型中，非结合胆红素以及胆红素葡萄糖醛酸酯可通过肝血窦膜进行双向转运。由于在吉尔伯特综合征和溶血性高胆红素血症患者中发现了典型的血清胆红素模式，因此测定血清中酯化胆红素对研究非结合性高胆红素血症的病理生理学和鉴别诊断具有重要价值。
