ENDOTHELIN AND OXIDANT STRESS IN CEREBRAL VASOSPASM

脑血管痉挛中的内皮素和氧化应激

• 批准号: 2750770
• 负责人: Robert Loughlin Macdonald
• 金额: $ 10.79万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-30 至 2000-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2750770
• 关键词: cerebral palsy; endothelin; enzyme activity; enzyme induction /repression; enzyme mechanism; ferritin; heme oxygenase; hemoglobin; hemolysis; hemoprotein; immunocytochemistry; laboratory rat; messenger RNA; oxidative stress; polymerase chain reaction; tissue /cell culture; vascular smooth muscle; vasospasm; western blottings

Cerebral vasospasm is delayed onset of vasoconstriction occurring days after aneurysmal subarachnoid hemorrhage. It is a major cause of stroke and death after subarachnoid hemorrhage. Hemoglobin and oxidant stress induced by it may be important in the pathogenesis of vasospasm. We found that heme oxygenase-1 messenger ribonucleic acid (mRNA) and protein are increased in smooth muscle cells exposed to hemoglobin. Heme oxygenase-1 protein is also increased in vasospastic arteries. Heme oxygenase-1 expression is known to be induced by oxidative stress and by heme in other types of cells, where it may protect against these cytotoxic stimuli. The long-term objective of this work is to determine the role of heme oxygenase-1 in vasospasm. The specific aims are: (1) To define the time course and dose-dependence of induction of heme oxygenase-1 and ferritin mRNA and protein in response to hemolysate and purified hemoglobin in cultured cerebrovascular smooth muscle cells. Hypothesis: Heme oxygenase-1 and ferritin are induced by solutions that contain heme, such as hemolysate and purified hemoglobin. (2) To define the time course of induction of heme oxygenase- 1 and ferritin mRNA and protein in the rat basilar artery after subarachnoid hemorrhage. Hypothesis: Vasospasm is associated with hemolysis, exposure of smooth muscle cells to heme, and induction of heme oxygenase-1 and ferritin. The induction of heme oxygenase-1 and ferritin is associated with the resolution of vasospasm. (3) To determine the effects of induction of heme oxygenase-1 and ferritin on vasospasm. Hypothesis: Induction of heme oxygenase-1 and ferritin decrease vasospasm.

脑血管痉挛是血管收缩发作的延迟天数 动脉瘤性蛛网膜下腔出血后。它是中风的主要原因之一。 蛛网膜下腔出血后死亡。血红蛋白与氧化应激 其诱导的血管痉挛可能在血管痉挛的发病机制中起重要作用。我们发现 血红素氧合酶-1信使核糖核酸(MRNA)和蛋白质是 暴露于血红蛋白的血管内皮细胞数量增加。血红素加氧酶-1 血管痉挛动脉中的蛋白质也会增加。血红素加氧酶-1 已知的表达是由氧化应激和其他 不同类型的细胞，在那里它可以保护免受这些细胞毒性刺激。这个 这项工作的长期目标是确定血红素的作用 加氧酶-1与血管痉挛具体目标是： (1)明确血红素诱导的时间进程和剂量依赖关系 氧合酶-1和铁蛋白对溶血和铁蛋白的反应 培养的脑血管平滑肌细胞中的纯化血红蛋白。 假设：血红素加氧酶-1和铁蛋白是由下列溶液诱导的 含有血红素，如溶血物和纯化的血红蛋白。 (2)明确血红素加氧酶-1诱导的时间进程和 蛛网膜下腔后大鼠基底动脉铁蛋白的表达 大出血。假设：血管痉挛与溶血、暴露有关 血管平滑肌细胞对血红素的诱导，以及对血红素加氧酶-1和 铁蛋白。血红素加氧酶-1和铁蛋白的诱导相关 随着血管痉挛的消退。 (3)检测血红素加氧酶-1和铁蛋白的诱导作用 关于血管痉挛。假设：血红素加氧酶-1和铁蛋白的诱导 减少血管痉挛。