Possible involvement of active oxygen species on the patients with homocystinuria and the infants with respiratory distress syndrome

活性氧可能与高胱氨酸尿症患者和呼吸窘迫综合征婴儿有关

• 批准号: 03670513
• 负责人: OGIHARA Tohru
• 金额: $ 1.28万
• 依托单位: Osaka Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670513/
• 关键词: Homocystinuria; LDL; Active Oxygen Species; Free Radical; Lipid Peroxidation; Allantoin; Uric Acid; Respiratory Distress Syndrome; 酸化LDL; デヒドロアスコルビン酸; 新生児仮死; フリ-ラジカル; 酸化変性LDL; ビタミンE

1).Homocystinuria : Homocystinuria is an inborn error of methionine metabolism that is characterized by the premature development of arteriosclerosis. As one of the major factors in the pathogenesis of arteriosclerosis, modification of low-density lipoprotein (LDL) has received widespread attention by many investigators. In this study, to elucidate the relationship between elevated homocysteine levels and premature arteriosclerosis, we investigated the role of homocysteine in the iron-catalyzed oxidative modification of LDL.When we incubated homocysteine with ferric iron, the content of sulfhydryl groups gradually decreased, and both superoxide and ferrous ion formed gradually. In this reaction thiobarbituric acid-reactive substances (TBARS) and fluorescent substances were formed, and the fragmentation of apoprotein B(apo-B) occured. The extent of oxidative modification was dependent on the concentration of homocysteine. Modification of LDL was suppressed until alpha-tocopherol consump … More tion reached a critical level. When the alpha-tocopherol content of LDL was increased 2.6 fold, both the formation of TBARS and the fragmentation of apo-B were suppressed to some extent. These results suggest that homocysteine might promote iron-catalyzed oxidation of LDL, and endogenous alpha-tocopherol can protect LDL against oxidative modification.2).Respiratory distress syndrome : We measured plasma allantion concentration as a proposal marker for free radical generation in 11 premature infants with respiratory distress syndrome (RDS) and 11 without RDS (non-RDS). Plasma allantoin level in RDS infants between 3 and 12 hours of life was significantly higher than that in non-RDS infants, although no significant difference was found in two groups within 3 hours after birth. These observation suggests that some oxidants are acturelly generated in the aqueous phase of plasma in RDS infants and the measurement of allantoin may be a useful indicator for free radical involvement in neonates. Less

1).同型胱氨酸尿症：同型胱氨酸尿症是一种先天性的蛋氨酸代谢缺陷，其特征是动脉硬化的过早发展。低密度脂蛋白（LDL）作为动脉粥样硬化发病机制中的主要因素之一，其修饰已受到研究者的广泛关注。本研究旨在探讨同型半胱氨酸在铁催化氧化修饰LDL中的作用，以阐明同型半胱氨酸水平升高与动脉粥样硬化的关系。反应中生成硫代巴比妥酸反应物（TBARS）和荧光物质，脱辅基蛋白B（apo-B）发生断裂。氧化修饰的程度取决于同型半胱氨酸的浓度。LDL的修饰被抑制，直到α-生育酚消耗。 ...更多信息 达到了临界水平。当LDL的α-生育酚含量增加2.6倍时，TBARS的形成和apo-B的断裂都在一定程度上受到抑制。这些结果表明，同型半胱氨酸可能促进LDL的铁催化氧化，内源性α-生育酚可以保护LDL免受氧化修饰。2）呼吸窘迫综合征：我们测定了11例呼吸窘迫综合征（RDS）早产儿和11例非RDS早产儿的血浆尿囊素浓度，作为自由基生成的一个建议标志物。出生后3 ~ 12 h RDS组血浆尿囊素水平显著高于非RDS组，但3 h内两组间差异无显著性。提示RDS患儿血浆水相中确实存在氧化剂，测定尿囊素可作为反映新生儿自由基参与程度的一个有用指标。少

项目成果

玉井 浩: "高令者における血漿,血球,頬粘膜細胞中のα-トコフェロール濃度の検討" ビタミン. 67. 17-21 (1993)

Hiroshi Tamai：“老年受试者血浆、血细胞和颊粘膜细胞中 α-生育酚浓度的研究”维生素。67. 17-21 (1993)

平野量哉: "ホモシスチン尿症における脂質過酸化の役割" フリーラジカルの臨床. 8. 85-89 (1994)

Yoshiya Hirano：“脂质过氧化在高胱氨酸尿症中的作用”自由基诊所。8. 85-89 (1994)

美濃 真: "新生児のビタミンE栄養状態の検討" ビタミン. 66. 527-531 (1992)

Makoto Mino：“新生儿维生素E营养状况的研究”维生素66。527-531（1992）

Kazuya Hirao: "Homocysteine induces iron-catalyzed lipid peroxidation of LDL that is prevented by α-tocopherol" Free Radical Research. (in press).

Kazuya Hirao：“同型半胱氨酸诱导铁催化的 LDL 脂质过氧化反应，可通过 α-生育酚预防”自由基研究（正在出版）。

美濃 真: "新生児のビタミンE栄養状態の検討" ビタミン. 66. 527-532 (1992)

Makoto Mino：“新生儿维生素E营养状况的研究”维生素66。527-532（1992）