权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Profile Analysis of Fetal Bile Acids and Congenital Liver Diseases

胎儿胆汁酸与先天性肝病的概况分析

基本信息

批准号：
62570970
负责人：
TOHMA Masahiko
金额：
$ 1.22万
依托单位：
Health Sciences University of Hokkaido
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1989
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-62570970/
关键词：
Fetal bile acid Congenital biliary atresia Gas chromatography-mass spectrometry High-performance liquid chromatography Immunoassay 1 beta-Hydroxylated bile acid Neonate Bile acid profile ガスクロマトグラフィ-質量分析 1β-水酸化胆汁酸 6ー水酸化胆汁酸 C_<27>ー胆汁酸

项目摘要

(1) The 1 beta- and 6 alpha-hydroxylated and DELT^A5-unsaturated bile acids were synthesized from cholic acid as a starting material, and these unusual bile acids were identified from meconium, amniotic fluid and neonatal urine. A highly sensitive and specific quantitative assay of these bile acids was developed by selected ion monitoring in GC-MS. The conjugated fetal bile acids were determined by HPLC using 3alpha-hydroxysteroid dehydrogenase and chemical luminesscence.(2) In profile analysis of fetal bile acids, 1 beta-hydroxylated cholic acid was predominant in full term amniotic fluid, and neonatal urine, while 6alpha-hydroxylated chenodeoxycholic acid constituted a main component in meconium. Quantity of these bile acids increased according to the progress of gestation and decreased with developmental age after birth. Taurine conjugates are main bile salts in meconium and were exchanged progressively for the glycine conjugates in neonatal biles.(3) Anti-fetal bile acid antisera were prepared by immunizing rabbits with hapten-bovine serum albumin conjugates coupled at C-15alpha and C-24 positions on the bile acid molecule, and their properties were investigated by heterologous combination assay using ^<125>I-labeled tracer. The antisera raised against these conjugates showed satisfactory affinity constants and reasonable specificity.(4) The metabolism of fetal bile acids was studied on congenital and cholestatic liver diseases. These results suggested that hydroxylation at C-1beta or C-6alpha position and conjugation with taurine in liver might be carried out for the elimination of bile acids in fetal period and cholestasis.

(1)以胆酸为原料合成了1 β -和6 α -羟基化胆汁酸和DELT^ a5不饱和胆汁酸，并从胎粪、羊水和新生儿尿液中鉴定出这些不寻常的胆汁酸。采用气相色谱-质谱联用技术对这些胆汁酸进行了选择性离子监测，建立了一种高灵敏度和特异性的定量分析方法。采用3 -羟基类固醇脱氢酶和化学发光相结合的高效液相色谱法测定共轭胎儿胆汁酸。(2)胎儿胆汁酸谱分析显示，足月羊水和新生儿尿中以1 -羟基化胆酸为主，胎便中以6 -羟基化鹅去氧胆酸为主。这些胆汁酸的数量随着妊娠的进展而增加，随着出生后的发育年龄而减少。牛磺酸缀合物是胎粪中主要的胆盐，在新生儿胆汁中逐渐被甘氨酸缀合物所交换。(3)将半抗原-牛血清白蛋白偶联物偶联于胆汁酸分子的c - 15α和C-24位点，免疫家兔制备抗胎儿胆汁酸抗血清，并用^<125> i标记示踪剂进行异源联合试验，研究其抗胎儿胆汁酸抗血清的性质。对这些偶联物制备的抗血清具有满意的亲和常数和合理的特异性。(4)研究先天性和胆汁淤积性肝病对胎儿胆汁酸代谢的影响。这些结果表明，肝脏中c -1 β或c -6 α位置的羟基化和与牛磺酸的结合可能在胎儿期消除胆汁酸和胆汁淤积。