ENDOTHELIN AND OXIDANT STRESS IN CEREBRAL VASOSPASM

脑血管痉挛是指血管收缩延迟发作， 是蛛网膜下腔出血后它是中风的主要原因 和蛛网膜下腔出血后死亡血红蛋白和氧化应激 可能在血管痉挛的发病机制中起重要作用。我们发现 血红素加氧酶-1信使核糖核酸（mRNA）和蛋白质是 在接触血红蛋白的平滑肌细胞中增加。血红素氧合酶-1 蛋白质在血管痉挛的动脉中也增加。血红素氧合酶-1 已知表达是由氧化应激和血红素诱导的， 细胞类型，在那里它可以保护免受这些细胞毒性刺激。的 这项工作的长期目标是确定血红素的作用 氧合酶-1在血管痉挛中的作用。具体目标是： (1)确定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和蛋白质对溶血产物的反应， 纯化血红蛋白在培养的脑血管平滑肌细胞。 假设：血红素加氧酶-1和铁蛋白是由溶液诱导的， 含有血红素，如溶血产物和纯化的血红蛋白。 (2)确定血红素氧合酶-1诱导的时间过程， 蛛网膜下腔阻滞对大鼠基底动脉铁蛋白mRNA和蛋白表达的影响 出血假设：血管痉挛与溶血、暴露相关 平滑肌细胞血红素，诱导血红素氧合酶-1和 铁蛋白血红素氧合酶-1和铁蛋白的诱导与 血管痉挛的消退 (3)确定血红素氧合酶-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。

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.