PROFILE OF FETAL BILE ACIDS IN FETUS AND NEONATE, THEIR CONGENITAL DIORDERS

胎儿和新生儿的胆汁酸代谢被认为与成人不同。尿胆汁酸谱已用于诊断由遗传缺陷引起的疾病，遗传缺陷导致胆汁酸代谢不完全。需要一种高灵敏度的方法来阐明新生儿尿液和血清中胆汁酸及其结合物的组成。(1)进行了2 β-、4 β-和19-羟基胆汁酸的合成，还合成了1和4-不饱和3-氧代丙酸作为标准物质。通过与上述标准品的比较，实现了对新生儿尿液中这些酸的鉴别。(2)胎儿-新生儿期胆汁酸谱显示，1 β-羟基胆酸从35周开始随妊娠进展而增加，并随发育年龄下降至出生后3岁。(3)建立了一种高效液相色谱-化学发光法测定尿中结合型1 β-和6 α-羟基胆汁酸的方法。(4)在胆酸和鹅去氧胆酸与猴肝微粒体的孵育混合物中检测到胆汁酸的1 β-羟基化。(5)本文采用毛细管气相色谱-质谱（GC-MS）负离子化学电离选择离子监测，建立了测定新生儿血清和干血斑片中胎儿胆汁酸的高灵敏度GC-MS方法。

The metabolism of bile acids in fetus and neonate is thought to be different from that in adults. A urinary bile acid profile has been used in the diagnosis of disease caused by genetic defects leading to the incomplete metabolism of bile acids. A highly sensitive method has been required to elucidate the composition of bile acids and their conjugates in neonatal urine and serum.(1) Synthesis of 2beta-, 4beta- and 19-hydroxy bile acids were carried out and 1 and 4-unsaturated 3-oxobile acids were also synthesized for the standard materials. The identification of these acids in urine from newborns were achieved by the comparison with above standards.(2) Profiles of bile acids infetal-neonatal periods showed that 1beta-hydroxy-cholic acid increased according to the progress of gestation from 35 weeks, and decreased with developmental age to 3y old after birth.(3) A quantitative analysis of the conjugated 1beta- and 6alpha-hydroxy bile acids in urine has been developed using HPLC with chemiluminescence detection.(4) The 1beta-hydroxylation of bile acids was detected in the incubation mixture of cholic and chenodeoxycholic acids with monkey liver microsome.(5) A highly sensitive GC-MS determination of the fetal bile acids in neonatal serum and dry blood spot disc has been developed by capillary GC-MS using selected ion monitoring with negative ion chemical ionization.