DEVELOPMENT OF BILIRUBIN TRANSPORT AND METABOLISM IN NEWBORN RHESUS-MONKEY
DEVELOPMENT OF BILIRUBIN TRANSPORT AND METABOLISM IN NEWBORN RHESUS-MONKEY
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DOI：
10.1016/s0022-3476(77)80360-0
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发表时间：
1977-01-01
影响因子：
5.1
通讯作者：
ZARAFU, I
中科院分区：
文献类型：
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作者：
GARTNER, LM;LEE, KS;ZARAFU, I
研究了足月猕猴、早产儿和后生猕猴（恒河猴）的肝脏转运和胆红素代谢。在未经治疗的新生儿中，观察到生理性非共轭高胆红素血症的双相模式。I期的特点是血清胆红素浓度在19小时内迅速上升到4.5 mg/dl，在48小时内同样迅速下降到1.0 mg/dl。II期的特点是在48-96小时内稳定升高1.0 mg/dl（比成人高4倍），随后下降到正常成人浓度。在29个正常的足月人类新生儿中也观察到相同的模式，但每个阶段的持续时间大约是猴子的3倍。I期高胆红素血症似乎是由于新生儿期肝脏胆红素负荷增加6倍，加上肝胆红素结合明显缺乏，这是I期的限速步骤。肝脏摄取胆红素在I期不限速，但可能导致II期高胆红素血症。在猴子出生后的头19天里，胆红素负荷持续增加。期生理性黄疸在猴新生儿完全消除产前母体和新生儿给予苯巴比妥。在I期，肝结合胆红素（葡萄糖醛酸转移酶活性）的3倍增强完全解释了高胆红素血症的预防。胆红素负荷不受苯巴比妥的影响。而在对照组新生儿中，胆红素负荷略高于肝脏胆红素偶联能力，导致胆红素滞留，在苯巴比妥治疗的新生儿中，肝脏偶联能力略高于胆红素负荷所需的水平。施用苯巴比妥不能改变II期高胆红素血症，也不能提高胆红素的最大肝脏摄取或排泄。肝葡萄糖醛酸转移酶活性在II期和新生儿期的剩余时间内增加了3倍。早产延缓了肝脏葡萄糖醛酸转移酶活性的成熟。在1例苯巴比妥治疗的早产猴新生儿中，对治疗没有明显的反应。在1个成熟后的猴新生儿中观察到胆红素摄取、结合和排泄的加速成熟。
Hepatic transport and metabolism of bilirubin were examined in term, premature and postmature newborn Macaca mulatta (rhesus) monkeys with and without prior phenobarbital treatment of pregnant mother and neonate. In untreated neonates a biphasic pattern of physiologic unconjugated hyperbilirubinemia was observed. Phase I was characterized by a rapid increase in serum bilirubin concentration to 4.5 mg/dl by 19 h and an equally rapid decline to 1.0 mg/dl by 48 h of age. Phase II was characterized by a stable elevation at 1.0 mg/dl (4 times greater than in the adult) from 48-96 h of age, followed by a decline to normal adult concentrations thereafter. An identical pattern was observed in 29 normal, term human neonates, but the duration of each phase was approximately 3 times as long as that in the monkey. Phase I hyperbilirubinemia appears to result from a 6-fold increase in bilirubin load presented to the liver in the neonatal period, combined with marked deficiency in hepatic bilirubin conjugation, the rate-limiting step during Phase I. Hepatic uptake of bilirubin is not rate limiting during Phase I but may contribute to Phase II hyperbilirubinemia. An increased bilirubin load persists throughout the first 19 days of life in the monkey. Phase I physiologic jaundice in the monkey neonate was completely eliminated by prenatal maternal and neonatal administration of phenobarbital. A 3-fold enhancement of hepatic conjugation of bilirubin (glucuronyl transferase activity) during Phase I entirely accounted for the prevention of hyperbilirubinemia. The bilirubin load was unaffected by administration of phenobarbital. Whereas in control neonates the bilirubin load slightly exceeded hepatic bilirubin conjugating capacity and resulted in retention of bilirubin, in phenobarbital-treated neonates, hepatic conjugating capacity slightly exceeded that required for the bilirubin load. Administration of phenobarbital failed to alter Phase II hyperbilirubinemia and did not enhance either maximal hepatic uptake or excretion of bilirubin. Hepatic glucuronyl transferase activity was increased 3-fold during Phase II and during the remainder of the neonatal period. Premature birth retarded maturation of hepatic glucuronyl transferase activity. In 1 phenobarbital-treated premature monkey neonate, there was no apparent response to treatment. Accelerated maturation of bilirubin uptake, conjugation and excretion of bilirubin was observed in 1 postmature monkey neonate.