乙醛脱氢酶2与硝酸酯耐药关系的研究进展

Progress in Research in Role of Mitochondrial Aldehyde Dehydrogenase in Nitrate Tolerance

从19世纪后期开始,硝酸酯类药物就应用于稳定型心绞痛、急性心肌梗死及慢性充血性心力衰竭的临床治疗。然而,长期应用时机体血管很快对其产生耐药,影响了该类药物的血流动力学和抗缺血效果。其耐药机制极为复杂,尚不十分清楚。近来研究表明,线粒体内活性氧簇的产生和继发乙醛脱氢酶2的氧化失活,在硝酸酯耐药和交叉耐药产生过程中起重要作用。

Organic nitrates are a group of very effective anti-ischcmic drugs used for the treatment of patients with stable angina, acute myocardial infarction and chronic congestive heart failure. Long-term therapy with organic nitrates, however, results in a rapid development of nitrate tolerance, thus blunting their hemodynamic and anti-ischemic efficacy. Recent studies have revealed that mitochondrial reactive oxygen species formation and a subsequent oxidative inactivation of the mitochondrial aldehyde dehydrogenase play an important role in the development of both nitrate and cross tolerance.