硝酸酯类的生物转化及其耐受机制的研究进展

Progresses in nitrate biotransformation and tolerance mechanisms

硝酸酯类的生物转化涉及谷胱甘肽转移酶、细胞色素P450代谢酶、黄嘌呤氧化酶和线粒体醛脱氢酶等多种酶,其中线粒体醛脱氢酶的作用引人注目;硝酸酯类耐受的机制包括巯基耗竭学说、神经激素激活学说和氧化应激学说等,其中氧化应激学说比较流行;对于硝酸酯类耐受的防治除补充巯基供体等传统方法外,一些具有抗氧化特性的药物如肼屈嗪和硫辛酸等具有良好的抗硝酸酯耐受作用,其机制与恢复被抑制的线粒体醛脱氢酶活性有关。因此,抗氧化治疗特别是寻找和开发针对恢复线粒体醛脱氢酶活性的抗氧化药物成为目前防治硝酸酯类耐受的新策略。

There are many enzymes including glutathione transferases, cytochrome P450 （ CYP450 ）, xanthine oxidase and mitochondrial aldehyde dehydrogenase that involve in the nitrate biotransformation. Among them, mitochondrial aldehyde dehydrogenase has been attracted special attention. Several theories including thiol depletion, activation of neurohormone and oxidative stress have been put forward to explain the phenomena of nitrate tolerance. Among them, oxidative stress theory is the current focus. In addition to the traditional thiol donors, some drugs with antioxidant property such as hydralazine and thioctic acid have been tried to treat nitrate tolerance and achieved good results, which was related to the reverse of inhibited mitochondrial aldehyde dehydrogenase. Therefore, to seek novel antioxidants which are able to improve mitochondrial aldehyde dehydrogenase activity is the new strategy for prevention of nitrate tolerance.