Clinical and experimental studies on cerebral vasospasm with reference to mechanism and treatment

脑血管痉挛的临床及实验研究及其机制及治疗参考

• 批准号: 01570804
• 负责人: YAMADA Hiromu
• 金额: $ 0.83万
• 依托单位: Gifu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1991
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-01570804/
• 关键词: Subarachnoid hemorrhage; Cerebral vasospasm; Leukotriene; Oxyhemoglobin; Cystosolic calcium; Phospholipase C; 細胞内カルシウムイオン; イノシト-ルリン脂質特質的ホスホリパ-ゼC; 破裂脳動脈瘤; アラキドン酸; 細胞内遊離カルシウム; GTPー結合蛋白質; イノシト-ルリン脂質特異的ホスホリパ-ゼ; アラキドレ酸

The purpose of this study was to clarify the role and action of leukotriene, arachidonic acid and lipid metabolites in the mechanism of cerebral vasospasm following aneurysmal subarachnoid hemorrhage(SAH). The following results were obtained : (1) In the experimental SAH, vertebral angiogram showed a tripple phase reaction of canine basal arteries caused by the intrathecal injection of leukotriene C_4. (2)In cultured rat vascular smooth-muscle cells, changes in the concentration of cytosolic calcium([Ca^*]i)before and after exposure to spasmogenic factors were measured. Leukotriene C_4 induced a slow, transient increase of[Ca^*]i. Oxyhemoglobin induced a significant elevation of[Ca^*]i which was sustained for 10 minites. (3)In the CSF of SAH patients, there is a marked elevation of the content of membrane lipids, and the activity of phospholipase C was enhanced in proportion to clinical grade according to Hunt and Hess during the early period after SAH. (4)The CSF of SAH patients induced significantly higher transient intracellular calcium elevations when compared to those induced by control CSF. Changes in intracellular free calcium elevations induced by CSF showed a biphasic response with highest concentration on Day 2 and 11 after SAH.The results suggested that some substances which induce the re-elevation of intracellular calcium concentrations in vascular smooth-muscle cells may be the key substances responsible for cerebral vasospasm.

本研究的目的是阐明白三烯、花生四烯酸和脂质代谢产物在蛛网膜下腔出血（SAH）后脑血管痉挛机制中的作用。结果表明：（1）在实验性SAH中，椎动脉造影显示鞘内注射白三烯C_4引起的犬基底动脉三相反应。(2)In培养的大鼠血管平滑肌细胞，测定暴露于致痉挛因子之前和之后细胞内钙浓度（[Ca^*]i）的变化。白三烯C_4引起[Ca^*]i缓慢、短暂的增加。氧合血红蛋白诱导[Ca^*]i显著升高，并持续10分钟。(3)In SAH患者脑脊液中膜脂含量在SAH后早期明显升高，磷脂酶C活性随Hunt和Hess临床分级而增高。（4）SAH患者CSF引起的一过性细胞内钙升高明显高于对照组。脑脊液引起的细胞内游离钙升高呈双相反应，以SAH后第2天和第11天浓度最高，提示引起血管平滑肌细胞内游离钙浓度再升高的某些物质可能是脑血管痉挛的关键物质。

项目成果

西村 康明 他: "脳血管攣縮に対する塩酸ジゼラップの効果ー特に髄液中リン脂質代謝との関係ー" 脳血管攣縮. 5. 179-183 (1990)

Yasuaki Nishimura 等：“吉塞拉普盐酸盐对脑血管痉挛的影响 - 特别是其与脑脊液磷脂代谢的关系”脑血管痉挛 5. 179-183 (1990)。

Katsunobu Takenaka: "Intracellular Ca changes in cultured vascular smooth muscle cells by treatment with various spasmogens." Neurological Research.

Katsunobu Takenaka：“通过用各种痉挛原治疗，培养的血管平滑肌细胞中的细胞内 Ca 发生变化。”

西村 康明他: "脳血管攣縮に対する塩酸ジラゼップの効果ー特に髄液中リン脂質代謝との関係ー" 脳血管攣縮. 5. 179-183 (1990)

Yasuaki Nishimura 等：“盐酸地西普对脑血管痉挛的影响 - 特别是其与脑脊液磷脂代谢的关系”Cerebral Vasospasm 5. 179-183 (1990)。

KATUNOBU TAKENAKA: "Induction of cytosolic free calcium elevation in rat vascular smoothーmuscle cells by cerebrospinal fluid from patients after subarachncid hemorrhage" Journal of Neurosurgery. 75. 452-457 (1991)

KATUNOBU TAKENAKA：“蛛网膜下腔出血后患者脑脊液诱导大鼠血管平滑肌细胞中胞质游离钙升高”《神经外科杂志》75。452-457（1991）。

Yasuaki Nishimura, Hideki Sakai, Masahiro Yanagimoto, Shin-ichi Shirakami, Makoto Iwamura, Kotoyuki Shimizu, Yoshiaki Miwa, Toshifumi Hirata, Takashi Andoh. Noboru Sakai, Hiromu Yamada, Akio Ohkuma, Tatsuaki Hattori: "Effects of Dilazep Dihydrochloride on

西村康明、酒井秀树、柳本雅宏、白神真一、岩村诚、清水琴行、美轮佳明、平田俊文、安藤隆。