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

胎儿和新生儿的胎儿胆汁酸概况及其先天性疾病

• 批准号: 02452268
• 负责人: TOHMA Masahiko
• 金额: $ 4.1万
• 依托单位: HIGASHI-NIPPON-GAKUEN UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1990
• 资助国家: 日本
• 起止时间: 1990 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-02452268/
• 关键词: FETAL BILE ACID; BILE ACID PROFILE; CONGENITAL DISORDER; CONJUGATED BILE ACID; GAS CHROMATOGRAPHY-MASS SPECTROMETRY; BILE ACID BIOSYNTHESIS; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; ガスクロマトグラフイー質量分析; 高速液体クロマトグラフイー; ガスクロマトグラフイ-質量分析; 高速液体クロマトグラフイ- /

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.

胎儿和新生儿胆汁酸的代谢被认为与成人不同。尿胆汁酸谱已被用于诊断由遗传缺陷导致胆汁酸代谢不完全引起的疾病。需要一种高度敏感的方法来阐明新生儿尿液和血清中胆汁酸及其缀合物的组成。(1)合成了2 -、4-和19-羟基胆汁酸，并合成了1和4-不饱和3-氧酸作为标准物质。通过与上述标准的比较，实现了新生儿尿液中这些酸的鉴定。(2)胎儿期-新生儿期胆汁酸谱显示，1 - β -羟基胆酸从35周开始随着妊娠的进展而升高，随着发育年龄的增长而下降，直至出生后3岁。(3)建立了用高效液相色谱-化学发光检测法定量分析尿液中共轭1 β -和6 α -羟基胆汁酸的方法。(4)测定了胆酸和鹅去氧胆酸与猴肝微粒体孵育液中胆汁酸的1 - β -羟基化。(5)建立了采用负离子化学电离选择性离子监测的毛细管气相色谱-质谱法测定新生儿血清和干血斑盘中胎儿胆汁酸的高灵敏度方法。

项目成果

Kaoru Obinata, Hiroshi Nittono, Keijiro Yabuta, Reijiro Mahara, and Masahiko Tohma: "1beta-Hydroxylated Bile Acids in the Urine of Healthy Neonates." J. Pediatr. Gastroenterol. Nutr.15, (1). 1-5 (1992)

Kaoru Obinata、Hiroshi Nittono、Keijiro Yabuta、Reijiro Mahara 和 Masahiko Tohma：“健康新生儿尿液中的 1β-羟基胆汁酸”。

Shigeo Ikegawa: "Measurement of Conjugated 1β-Hydroxycholic Acid in Urine of Newborns by Specific Radioimmunoassay." Chem.Pharm.Bull.40. 701-704 (1992)

Shigeo Ikekawa：“通过特定放射免疫测定法测定新生儿尿液中的结合 1β-羟基胆酸。”Chem.Pharm.Bull.40 (1992)。

Shigeo Ikegawa: "Conjugated 1β-Hydroxycholic Acid in the Urine of Newborns and Pregnant Women measured by Radioimmunoassay using Antisera raised against N-(1β-Hydroxycholyl)-2-aminopropionic Accid-BSA Conjugate." Chem.Pharm.Bull.40. 1835-1838 (1992)

Shigeo Ikekawa：“使用针对 N-(1β-羟基胆基)-2-氨基丙酸-BSA 结合物的抗血清，通过放射免疫测定法测量新生儿和孕妇尿液中的结合 1β-羟基胆酸。Chem.Pharm.Bull.40。” -1838 (1992)

Yoshinobu Hata: "Proc. 5th Intern. Sympo."Biliary Atresia"" Fetal Bile Acids in Congenital Biliary Atresia., 182-186 (1991)

Yoshinobu Hata：“Proc. 5th Intern. Sympo.“Biliary Atresia””先天性胆道闭锁中的胎儿胆汁酸。，182-186 (1991)

Akira Honda, Junichi Shoda, Naomi Tanaka, Yasushi Matsuzaki, Toshiaki Osuga, Nobuharu Shigematsu, Masahiko Tohma, and Hiroshi Miyazaki: "Simultaneous Assay of the Activities of Two Key Enzymes in Cholesterol Metabolism by Gas Chromatography-Mass Spectrome

Akira Honda、Junichi Shoda、Naomi Tanaka、Yasushi Matsuzaki、Toshiaki Osuga、Nobuharu Shigematsu、Masahiko Tohma 和 Hiroshi Miyazaki：“通过气相色谱-质谱法同时测定胆固醇代谢中两种关键酶的活性