ENDOTHELIN AND OXIDANT STRESS IN CEREBRAL VASOSPASM

脑血管痉挛中的内皮素和氧化应激

基本信息

批准号：
2891377
负责人：
Robert Loughlin Macdonald
金额：
$ 9.71万
依托单位：
UNIVERSITY OF CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
1996
资助国家：
美国
起止时间：
1996-09-30 至 2001-07-31
项目状态：
已结题

项目摘要

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.

脑血管痉挛延迟发生的几天血管收缩的发作动脉瘤性蛛网膜下腔出血后。这是中风的主要原因和蛛网膜下腔出血后的死亡。血红蛋白和氧化剂应激它引起的可能在血管痉挛的发病机理中很重要。我们发现血红素氧酶-1信使核糖核酸（mRNA）和蛋白质是暴露于血红蛋白的平滑肌细胞中增加。血红素氧酶-1 血管疗法动脉中的蛋白质也增加。血红素氧酶-1 已知表达是由氧化应激和血红素诱导的细胞的类型，可以防止这些细胞毒性刺激。这这项工作的长期目标是确定血红素的作用血管痉挛中的氧酶-1。具体目的是：（1）定义血红素诱导的时间过程和剂量依赖性氧合酶-1和铁蛋白mRNA和蛋白质响应溶血酸盐和蛋白质培养的脑血管平滑肌细胞中纯化的血红蛋白。假设：血红素氧酶-1和铁蛋白是由溶液诱导的含有血红素，例如血凝酸盐和纯化的血红蛋白。（2）定义血红素加氧酶-1的诱导时间过程和亚蛛网膜炎后大鼠基底动脉中的铁蛋白mRNA和蛋白质出血。假设：血管痉挛与溶血，暴露有关平滑肌细胞的血红素，以及血红素氧酶-1和铁蛋白。血红素加氧酶-1和铁蛋白的诱导是相关的通过血管痉挛的分辨率。（3）确定血红素加氧酶-1和铁蛋白的诱导影响关于血管痉挛。假设：血红素加氧酶-1和铁蛋白的诱导减少血管痉挛。