PROFILE OF FETAL BILE ACID IN FETUS AND NEONATE,AND DIAGNOSIS OF NEONATAL HEPATOBILIALY DISEASES

胎儿和新生儿的胎儿胆汁酸概况及新生儿肝胆疾病的诊断

• 批准号: 05671788
• 负责人: TOHMA Masahiko
• 金额: $ 1.34万
• 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: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05671788/
• 关键词: FETAL BILE ACID; BILE ACID PROFILE; NEONATAL LIVER DISTEASE; GAS CHROMATOGRAPHY-MASS SPECTROMETRY; BILE ACID ENZYMATIC BIOSYNTHESIS; HYPERTYROSINEMIA CHOLESTASIS; 3-0X0 UNSATURATED BILE ACID; RAT LIVER MICROSOME; 未熟児; 高速液体クロマトグラフィー; 胎児性胆汁酸合成; カ

The metabolism of bile acids in fetus and neonate is thought to be different from that in adults. A highly sensitive analytical metod of bile acids by GC-MS has been required to elucidate the composition of fetal bile acids in serum for the diagnosis of neonatal hepatobiliary diseases.(1) Symthesis of 4beta- and 6alpha-hydroxy bile acids were efficiently carried out for the identification of these acid in urine and serum from neonates by the comparison with the standards.(2) A higly sensitive GC-MS determination of the fetal bile acid in neonatal serum and dry blood spot disc has been developed by capillary GC-MS using selected ion monitoring with negative ion chemical ionization.(3) The fetal bile acids are usualy biosynthesized thrugh the hydroxylation at 1beta- or 6alpha-psition of the correspnding usual bile acids. The 1beta-hydroxylated C_<27>-bile acid were detected in the incubation mixture of the C_<27>-intermediates with rat liver microsome as a new biosynthetic route.(4) Diagnostic analysis of neonatal liver diseases was accomplished by GC-MS.The 3-oxo unsaturated bile acids were identified and determined in the urine of patients with sevear cholestasis from hypertyrosinemia.

胎儿和新生儿的胆汁酸代谢被认为与成人不同。为了解胎儿血清中胆汁酸的组成，用于新生儿肝胆疾病的诊断，需要一种高灵敏度的GC-MS分析方法。(1)通过与标准品的比较，有效地进行了4 β-和6 α-羟基胆汁酸的合成，用于鉴定新生儿尿液和血清中的这些酸。(2)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GC-MS方法。(3)胎儿胆汁酸的生物合成通常是通过相应的普通胆汁酸在1 β或6 α位的羟基化。在<27>C_ -胆汁酸中间体与大鼠肝微粒体的孵育混合物中发现了1 β-羟基化C_ -胆汁酸<27>，这是一条新的生物合成途径。(4)本文应用GC-MS对新生儿肝脏疾病进行了诊断分析，并对高酪氨酸血症致胆汁淤积症患儿尿中的3-氧代不饱和胆汁酸进行了鉴定和测定。

项目成果

Mizuho Une, Akihumi Inoue, Takao Kurosawa, Masahiko Tohma, and Takahiko Hoshita.: "Identification of (24E)-3alpha, 7alpha-Dihydroxy-5beta-cholest-24-enoic Acid and (24R,25S)-3alpha, 7alpha, 24-Trihydroxy-5beta-cholestanoic Acid as Intermediates in the Con

Mizuho Une、Akihumi Inoue、Takao Kurosawa、Masahiko Tohma 和 Takahiko Hoshita。：“(24E)-3α、7α-二羟基-5β-胆甾醇-24-烯酸和 (24R,25S)-3α、7α、24 的鉴定

Shigeo Ikegawa: "Redioimmunoassay of Conjugated 1β-Hydroxycholic Acid in Dried Blood Spots for Diagnosis of Congenital Biliary Atresia." Biol.Pharm.Bull.17. 5-8 (1994)

Shigeo Ikekawa：“干血斑中结合的 1β-羟基胆酸的重新免疫分析用于诊断先天性胆道闭锁。”5-8 (1994)。

Hitoshi Chiba: "A Direct Enzyme Immunoassay for 18-Hydroxycortisol in Urine : A New Tool for Screening Primary Aldosteronism." J. Steroid Biochem. Molec. Biol.46. 85-89 (1993)

Hitoshi Chiba：“尿液中 18-羟基皮质醇的直接酶免疫测定：筛查原发性醛固酮增多症的新工具。”

Takao Kurosawa, Hiroyuki Nakano, Masahiro Sato, Masahiko Tohma: "Synthesis of 3alpha, 3alpha, 12alpha-Trihydroxy-and 3alpha, 7alpha-Dihydroxy-5beta-cholestan-26-oic Acid by the Use of beta-Ketosulfoxide." Steroids.(in press). (1995)

Takao Kurosawa、Hiroyuki Nakano、Masahiro Sato、Masahiko Tohma：“使用 β-酮亚砜合成 3α、3α、12α-三羟基-和 3α、7α-二羟基-5β-胆甾坦-26-oic 酸。”

Shigeo Ikegawa: "Radioimmunoassay of Conjugated 1beta-Hydroxycholic Acid in Dried Blood Spots for Diagnosis of Congenital Biliary Atresia." Biol.Pharm.Bull.17. 5-8 (1994)

Shigeo Ikekawa：“干血斑中结合 1β-羟基胆酸的放射免疫分析用于诊断先天性胆道闭锁。”