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Role of oxidative stress in pathogenesis of coronary spasm, a molecular biological and clinical study

氧化应激在冠状动脉痉挛发病机制中的作用，分子生物学和临床研究

基本信息

批准号：
11670693
负责人：
KUGIYAMA Kiyotaka
金额：
$ 2.24万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

We examined the effect of reduced glutathione (GSH), an important antioxidant which restores intracellular redox imbalance and prevents inactivation of endothelial-derived nitric oxide, on the abnormal vasomotor reactivity in spasm coronary arteries. Responses of epicardial diameter of the left coronary arteries to intracoronary infusion of acetylcholine (ACh, 50μg/min) were measured by quantitative coronary angiography before and during combined intracoronary infusion of GSH (50mg/min, 6 min) or saline as a placebo in 24 patients with coronary spastic angina (CSA) and in 28 control patients. All of the spasm coronary arteries showed constrictor response to ACh, while the control coronary arteries as a whole showed only minimal diameter changes to ACh. GSH infusion suppressed constrictor response of epicardial diameter to ACh in patients with CSA, while it had no significant effect in control subjects. Saline infusion did not have any effects. The results indicate that GSH attenuated constrictor response to ACh in epicardial coronary arteries of patients with CSA.GSH may have an important role in the regulation of coronary vasomotor function in patients with CSA.Oxidized low-density lipoproteins (LDL) impair endothelium-dependent dilation and constrict arteries. This study examined possible relation of the circulating plasma levels of Ox-LDL to CSA.The plasma levels of Ox-LDL were measured by ELISA in 37 consecutive patients with CSA and normal coronary angiograms and in 79 consecutive control patients. The Ox-LDL levels in patients with CSA were significantly higher than those in controls. In multivariate analysis, higher levels of Ox-LDL were a risk factor for CSA independently of other traditional risk factors. The Ox-LDL levels had a significant and positive correlation with constrictor response of coronary arteries to the intracoronary acetylchnoline infusion. Thus, Ox-LDL may play a possible role in pathogenesis of coronary spasm.

还原性谷胱甘肽（GSH）是一种重要的抗氧化剂，可以恢复细胞内氧化还原失衡，防止内皮来源的一氧化氮失活，我们研究了还原性谷胱甘肽（GSH）对痉挛冠状动脉异常血管舒张反应性的影响。采用定量冠状动脉造影法测定24例冠心病痉挛性心绞痛（CSA）患者和28例对照患者冠脉内联合输注GSH （50mg/min, 6 min）或生理盐水（安慰剂）前后左冠状动脉心外膜直径对乙酰胆碱（ACh, 50μg/min）的反应。所有痉挛冠状动脉对乙酰胆碱均表现出收缩反应，而对照组冠状动脉对乙酰胆碱的直径变化很小。GSH输注抑制CSA患者心外膜直径对乙酰胆碱的收缩反应，而对对照组无显著影响。生理盐水输注无任何影响。结果表明，谷胱甘肽能减弱CSA患者心外膜冠状动脉对乙酰胆碱的收缩反应。谷胱甘肽可能在CSA患者冠状动脉血管舒缩功能的调节中起重要作用。氧化低密度脂蛋白（LDL）损害内皮依赖性扩张和动脉收缩。本研究探讨了循环血浆Ox-LDL水平与CSA的可能关系。采用酶联免疫吸附试验（ELISA）测定了37例CSA合并冠状动脉造影正常患者和79例对照患者的血浆Ox-LDL水平。CSA患者的Ox-LDL水平明显高于对照组。在多因素分析中，高水平的Ox-LDL是CSA的危险因素，独立于其他传统危险因素。Ox-LDL水平与冠状动脉对乙酰胆碱灌注的收缩反应呈显著正相关。因此，Ox-LDL可能在冠状动脉痉挛的发病机制中起作用。