ANALYSIS OF THE BILE ACID PROFILES AND APPLICATION TO THE CONGENITAL LIVER DISORDER

建立先天性肝脏疾病的诊断是治疗早期肝脏疾病的迫切需要。本研究的目的是通过GC-MS和免疫学方法对胎儿胆汁酸进行定量分析，阐明胆汁酸谱随生长的变化，建立先天性胆道闭锁的准确诊断和筛查方法。(1)化学<27>合成了胆酸和胆醇的立体异构体。新开发的分析这些中间体实现了毛细管气相色谱法。(2)建立了高灵敏度的放射免疫分析法和酶免疫分析法。用建立的方法检测了孕妇和新生儿尿中结合胎胆汁酸的变化。(3)新生儿期胆汁酸组成随生长而变化。在早产儿的情况下，观察到类似的结果。比较1 β-羟化酶与胆酸的比值，结果表明1 β-羟化酶活性随生长而降低。(4)1.一、应用酶免疫分析法对先天性胆道闭锁进行诊断分析。还检查了使用干血斑进行假阳性筛查的可能性。2.用GLC法对Zellweger综合征患者尿液中的THCA和Varanic酸进行了定性和定量分析。3.除1 β-羟基胆酸外，还发现1 β-羟基化C_<23>-和C_<22>-胆汁酸。

The establishment of the diagnosis of congenital liver disorder is urgently required for the remedy of liver disorder in early life. The aim of this research is the development of quantitative analysis of fetal bile acids by GC-MS and immunological assay, elucidation of the change of bile acid profiles with growth, and establishment of the precise diagnosis and masscreening of congenital biliary atresia.(1) The stereoisomeric C_<27>-bile acids and bile alcohols were chemically synthesized for the authentic specimens. The newly developed analysis of these intermediates was achieved by capillary gas chromatography.(2) Highly sensitive radioimmunoassay and enzyme immunoassay were developed. By the established method, the change of conjugated fetal bile acids in urine of pregnant women and newborns was examined.(3) The bile acid composition of neonatal periods changed with growth. In the case of preterm infants, the similar results were observed. The result of comparison of the ratio of 1beta-hydroxycholic acid to cholic acid indicated the activity of 1beta-hydroxylase decreased with growth.(4) 1. Diagnostic analysis of congenital biliary atresia was accomplished by enzyme immunoassay. The possibility of masscreening using dried blood spots was also examined. 2. From the urine of Zellweger syndrome, THCA and varanic acid were identified and determined by GLC. 3. In addition to 1beta-hydroxycholic acid, 1beta-hydroxylated C_<23>- and C_<22>-bile acids were found in the urine of patients with cerebrotendinous xantomatosis.