Function of Prostaglandin D Synthase in Cerebrospinal Fluid after Subarachnoid Hemorrhage / Application for the Treatment of Cerebral Vasospasm

蛛网膜下腔出血后脑脊液中前列腺素D合酶的作用/在治疗脑血管痉挛中的应用

• 批准号: 12671376
• 负责人: MASE Mitsuhito
• 金额: $ 2.05万
• 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: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671376/
• 关键词: subarachnoid hemorrhage; beta-trace; prostaglandin D synthase; cerebral vaspspasm; biliverdin

In order to test the hypothesis that lipocalin-type prostaglandin D synthase (PGDS) in cerebrospinal fluid (CSF) may trap or scavenge substances which cause cerevral vasospasm after subarachnoid (SAH) hemorrhage and reduce ischemic sequela, we performed experimental and clinical evaluations and obtained following results.(1) The PGDS level in lumbar CSF increased about 2-fold at day 3 and day 5. The transient and delayed increase in the PGDS level in CSF is due to its induction of PGDS in the arachnoid membrane after SAH.(2) The substance binding to PGDS in CSF of patients with SAH was shown to be biliverdin by GC mass spectroscopy.(3) Human recombinant PGDS injected into the subarachonoid space of dog was tranported to blood quickly and finall discharged into urine. PGDS injected into blood never went into CSF.(4) PGDS binding biliverdin was shown in urine of patients with SAH.(5) Biliverdin oxides was one of strong vasoconstrictors in vitro.(6) There was a tendency that intrathecal injection of PGDS might reduce the severity of vasospasm estimated by angiography using couble-injection SAH canine model.

为了验证脑脊液中脂质运载蛋白型前列腺素D合成酶（PGDS）可能捕获或抑制蛛网膜下腔出血（SAH）后引起脑血管痉挛的物质，减少脑缺血后遗症的假说，我们进行了实验和临床研究，获得了以下结果。(1)在第3天和第5天，腰椎CSF中的PGDS水平增加约2倍。脑脊液中PGDS水平的一过性和延迟性升高是由于其诱导SAH后蛛网膜中的PGDS。(2)GC质谱分析表明SAH患者脑脊液中PGDS的结合物为胆绿素。(3)将重组人PGDS注入犬蛛网膜下腔后，迅速转运至血液，最后经尿液排出。PGDS注射到血液中不会进入脑脊液。(4)SAH患者尿中可检测到PGDS结合胆绿素。(5)胆绿素氧化物是一种较强的离体血管收缩剂。(6)鞘内注射PGDS有减轻血管痉挛程度的趋势。

项目成果

Mase M. et al: "Changes in lipocalin-type Prostaglandin D synthase level in cerebrospinal fluid of patients with subarachnoid hemorrhage"Ssurgery for Cerebral Stroke. 29(Suppl)(in press).

Mase M.等人：“蛛网膜下腔出血患者脑脊液中脂质运载蛋白型前列腺素D合酶水平的变化”脑中风手术。

Urade Y. et al.: "Biochemical, structural, genitic, physiological, and pathophysiological features of lipocalin-type prostaglandin D synthase"Biochim Biophys Acta. 1432. 259-271 (2000)

Urade Y.等：“脂质运载蛋白型前列腺素D合酶的生物化学、结构、遗传、生理和病理生理学特征”Biochim Biophys Acta。

間瀬光人 他: "くも膜下出血後髄液中prostaglandfn D合成酵素(β-trace)の変化"脳卒中の外科(増刊号). 29(suppl)(印刷中).

Mitsuto Mase 等人：“蛛网膜下腔出血后脑脊液中前列腺素 D 合酶（β-痕量）的变化”《中风手术》（特刊）29（增刊）（出版中）。

Urade Y, et al.: "Biochemical, structural, genitic, physiological, and pathophysiological features of lipocalin-type prostaglandin D synthase"Biochim Biophys Acta. 1482. 259-271 (2000)

Urade Y 等：“脂质运载蛋白型前列腺素 D 合酶的生物化学、结构、遗传、生理和病理生理学特征”Biochim Biophys Acta。

間瀬光人 他: "くも膜下出血後髄液中prostaglandinD合成酵素(β-trace)の変化"脳卒中の外科(増刊号). 29(suppl)(印刷中).

Mitsuto Mase 等人：“蛛网膜下腔出血后脑脊液中前列腺素 D 合酶（β-痕量）的变化”《中风手术》（特刊）29（增刊）（印刷中）。