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

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SAH后其诱导蛛网膜PGDS的产生。(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。

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.