Role of prostaglandin D synthase in cerebrospinal fluid after subarachnoid hemorrhage, and its neuroprotective effect

蛛网膜下腔出血后脑脊液中前列腺素D合酶的作用及其神经保护作用

• 批准号: 14571327
• 负责人: MASE Mitsuhito
• 金额: $ 2.18万
• 依托单位: Nagoya City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571327/
• 关键词: Lipocalin-type prostaglandin D synthase; subarachnoid hemorrhage; cerebral vasospasm; biliverdin; normal pressure hydrocephalus; cerebrospinal fluid; neuroglobin; VEGF; ビリルビン

Lipocalin-type prostaglandin D synthase (L-PGDS) exists in the cerebrospinal fluid (CSF). We have shown that L-PGDS in CSF increased significantly at 3-5 days after subarachnoid hemorrhage (SAH) in human. The aim of this study is to clarity a role increased L-PGDS in SAH and its neuroprotective effect.The L-PGDS showed an absorbance spectrum with a peak at 392 nm in the visible range. There was a negative correlation between the amount of the binding pigments to L-PGDS and the enzyme activity of L-PGDS. Digested fragments of L-PGDS by endoproteinase Lys-C included heme breakdown products, biliverdin and its analogues, determined by mass spectrometry. On the other hand, recombinant human L-PGDS injected into canine CSF space was quickly secreted into the serum, and was excreted into the urine. T1/2 of L-PGDS injected into blood was about 10 minutes. L-PGDS acts as a scavenger of bile pigments such as biliverdin and its analogues which accumulate in the CSF after SAH to reduce neuronal damage due to SAH.We could not showed the significant difference of mRNA expression of L-PGDS in meninges of rat SAH model. We also could not get enough data showing relationship among PGDS, VEGF, and neuroglobin.We newly found that L-PGDS was a useful marker for the diagnosis of normal pressure hydrocephalus in human.

脂质运载蛋白型前列腺素D合成酶（L-PGDS）存在于脑脊液（CSF）中。我们发现，人蛛网膜下腔出血（SAH）后3-5天脑脊液中L-PGDS显著升高。本研究旨在阐明L-PGDS在SAH中的作用及其神经保护作用。与L-PGDS结合的色素量与酶活性呈负相关。通过质谱法测定，内切蛋白酶Lys-C消化的L-PGDS片段包括血红素分解产物、胆绿素及其类似物。另一方面，注射到犬CSF间隙中的重组人L-PGDS迅速分泌到血清中，并排泄到尿液中。L-PGDS的T1/2约为10 min。L-PGDS可清除SAH后脑脊液中胆色素如胆绿素及其类似物，减轻SAH所致的神经元损伤。PGDS与VEGF、脑红蛋白之间的关系尚缺乏足够的资料，我们新发现L-PGDS是诊断正常压力性脑积水的一个有用指标。

项目成果

間瀬光人, 山田和雄, 裏出良博: "髄液中くも膜下血腫代謝産物の排泄機構の解明草・lipocalin型prostaglandin D合意性酵素の役割"脳卒中の外科. 31(Suppl). 76-80 (2003)

Mitsuto Mase、Kazuo Yamada、Yoshihiro Urade：“阐明脑脊液中蛛网膜下腔血肿代谢物的排泄机制和脂质运载蛋白型前列腺素 D 酶的作用”31（增刊）。

Mase M.Yamada K, Urade Y: "Lipocalin-type prostaglandin D synthase (beta-trace) in cerebrospinal fluid; A useful marker for the diagnosis of normal pressure hydrocephalus"Neuroscience Research. 47. 455-459 (2003)

Mase M.Yamada K、Urade Y：“脑脊液中的脂质运载蛋白型前列腺素 D 合酶（β-痕量）；诊断正常压力脑积水的有用标记”神经科学研究。

間瀬光人, 山田和雄, 裏出良博: "髄液中くも膜下血腫代謝産物の排泄機構の解明・lipocalin型prostaglandin D合意性酵素の役割"脳卒中の外科. 31(Suppl). 76-80 (2003)

Mitsuto Mase、Kazuo Yamada、Yoshihiro Urade：“阐明脑脊液中蛛网膜下腔血肿代谢物的排泄机制和脂质运载蛋白型前列腺素D酶的作用”31（增刊）。

Mase M, Yamada K, Urade Y: "Lipocalin-type prostaglandin D synthase (beta-trace) in cerebrospinal fluid is a reliable diagnostic marker of normal pressure diagnosis from other dementia causing diseases."Proceeding of Japan Normal Pressure Hydrocephalus Me

Mase M、Yamada K、Urade Y：“脑脊液中的脂质运载蛋白型前列腺素 D 合酶（β-痕量）是正常压力诊断其他痴呆症引起的疾病的可靠诊断标志物。”日本常压脑积水 Me 论文集

間瀬光人, 山田和雄, 裏出良博: "正常圧水頭症と他の痴呆性疾患との鑑別診断マーカーとしての(bcta-trace)測定の有用性"正常圧水頭症研究会・研究発表報告集. 3. 85 (2003)

Mitsuto Mase、Kazuo Yamada、Yoshihiro Urade：“(bcta-trace) 测量作为正常压力脑积水和其他痴呆疾病之间的鉴别诊断标记的有用性”正常压力脑积水研究小组研究演示报告 .3.85 (2003)