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年人不同。尿胆酸谱已被用于诊断由导致胆汁酸代谢不完全的遗传缺陷引起的疾病。建立了一种高灵敏度的分析新生儿尿液和血清中胆汁酸及其结合物组成的方法：(1)合成了2β-、4-β和19-羟基胆汁酸，并合成了1和4-不饱和3-羟基胆汁酸作为标准品。(2)新生儿胆汁酸谱：1β-羟胆酸从35周开始随孕周增加而升高；(3)建立了尿液中结合胆汁酸和6α-羟基胆汁酸的高效液相色谱-化学发光法定量分析方法.(4)胆酸和鹅去氧胆酸与猴肝微球的孵育混合物中胆汁酸发生了1β-羟基化反应.(5)建立了毛细管气相色谱-质谱法测定新生儿血清和干血斑盘中胎儿胆汁酸的方法。

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.