A Research for Prophylaxis of Ischemia-Reperfusion Damage in the Brain of Neonates during Perinatal Period.

围产期新生儿脑缺血再灌注损伤预防研究。

• 批准号: 11671608
• 负责人: ITAKURA Atsuo
• 金额: $ 2.3万
• 依托单位: NAGOYA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671608/
• 关键词: HNE; PSN; Ishemic-reperfusion damage in brain

Four-hydroxynonenal (HNE) has been proposed as an important marker of radical-induced lipid peroxidation. To assess the occurrence of lipid peroxidation and subsequent neuronal cell death in perinatal brain was the principal objective of this study. Immunochemical studies using an antibody against HNE-modified protein were performed in controls aged from 20 weeks of gestation to 64 years, and patients with pontosubicular neuron necrosis (PSN). Immunohistochemical study showed developmental and aging changes of positive staining in Purkinje cells and pontine neurons (27 weeks - 7 months, 50, 64 years). In addition, karyorrhectic cells in pontine nuclei with PSN were positively stained. Immunoblotting revealed that the 75-kDa protein, which was speculated as mitochondrial complex-1 protein, was the most intensely expressed among multiple immunoreactive proteins. Our results indicated the presence of oxidative stress in the perinatal neuron, and this oxidative stress may contribute to karyorrhectic death.In addition fetal endothelial cells incubated in hypoxic condition increased the expression of angiotensin-converting enzyme which is a key enzyme of regulation of blood perfusion in fetus. In a next project we will research to elucidate the relation between rennin-angiotensin system and ischmic-reperfusion damage in the fetal brain.

四羟基壬烯醛（HNE）被认为是自由基诱导的脂质过氧化的重要标志物。本研究的主要目的是评估围产期脑中脂质过氧化和随后的神经细胞死亡的发生。使用HNE修饰蛋白的抗体进行免疫化学研究，年龄从20周到64岁的对照组和脑桥下托神经元坏死（PSN）患者。免疫组化显示浦肯野细胞和脑桥神经元阳性染色呈发育性和增龄性变化（27周~ 7个月、50岁、64岁）。此外，PSN桥脑核内的核出血细胞呈阳性染色。免疫印迹显示，75 kDa的蛋白质，这是推测为线粒体复合物-1蛋白，是最强烈的多种免疫反应性蛋白质中表达。本研究结果提示，胎儿内皮细胞在缺氧条件下存在氧化应激，这种氧化应激可能是导致核出血性死亡的原因之一，同时，缺氧条件下培养的胎儿内皮细胞表达血管紧张素转换酶，这是调节胎儿血液灌注的关键酶。本课题将进一步研究肾素-血管紧张素系统与胎脑缺血再灌注损伤的关系。

项目成果

Y.Hariyama,A.Itakura,et al.: "Placental Aminopeptidase A as a Possible Barrier of Angiotensin II between Mother and Fetus."Placenta. (in press). (2000)

Y.Hariyama、A.Itakura 等人：“胎盘氨基肽酶 A 作为母亲和胎儿之间血管紧张素 II 的可能屏障。”胎盘。

H.Nakamura, et al.: "Oxytocin stimulates the translocation of oxytocinase of human vascular endothelial cells via activation of oxytocin receptors."Endocrinology. 141. 4481-4485 (2000)

H.Nakamura 等人：“催产素通过激活催产素受体刺激人血管内皮细胞催产素酶的易位。”内分泌学。

Y.Hariyama et al.: "Placental Aminopeptidase A as a Possible Barrier of Angiotensin II between Mother and Fetus"Placenta. 21. 621-627 (2000)

Y.Hariyama 等人：“胎盘氨基肽酶 A 作为母亲和胎儿之间血管紧张素 II 的可能屏障”胎盘。

Y.Hariyama et al.: "Placental Aminopeptidase A as a Possible Barrier of Angiotensin II between Mother Fetus"Placenta. 21. 621-627 (2000)

Y.Hariyama 等人：“胎盘氨基肽酶 A 作为母体胎儿之间血管紧张素 II 的可能屏障”胎盘。

H.Nakamura et al.: "Oxytocin Stimulates the Translocation of Oxytocinase of Human Vascular Endothelial Cells Via Activation of Oxytocin Receptors"Endocrinology. 141. 4481-4485 (2000)

H.Nakamura 等人：“催产素通过激活催产素受体刺激人血管内皮细胞催产素酶的易位”内分泌学。