甘草酸及其苷元甘草次酸盐皮质激素样作用研究进展_张明发.pdfVIP

• 448 • 现代药物与临床 Drugs Clinic 第 26 卷 第 6 期 2011 年 11 月 甘草酸及其苷元甘草次酸的盐皮质激素样作用研究进展 张明发，沈雅琴 上海美优制药有限公司，上海 201422 摘 要：甘草酸在体内水解成甘草次酸，甘草次酸的化学结构类似于甾体激素，因此甘草酸是甘草次酸的前体药物。甘草酸 和甘草次酸是甾体激素代谢失活酶（尤其是Ⅱ型 11β-羟化甾体脱氢酶）抑制剂，可提高内源性和外源性皮质激素的活性。 甘草酸和甘草次酸又可作为配体，与皮质激素受体结合呈现出糖皮质激素、盐皮质激素样作用。因此长期使用甘草或甘草酸 类药物产生的盐皮质激素样作用可用于艾迪生病的治疗，但用于其他疾病治疗时，盐皮质激素样作用就有可能成为不良反应 （主要表现为假性醛固酮增多症或高血压），约占甘草和甘草酸类药物不良反应的 50% 以上；并对其引起假性醛固酮增多症 或高血压的机制进行了讨论。 关键词：甘草酸；甘草次酸；盐皮质激素样作用；假性醛固酮增多症；高血压 中图分类号：R282.71 文献标志码：A 文章编号：1674 - 5515(2011)06 - 0448 - 05 Advances in studies on mineralocorticoid-like effect of glycyrrhizic acid and its aglycone glycyrrhetic acid ZHANG Ming-fa, SHEN Ya-qin Shanghai Meiyou Pharmaceutical Co., Ltd., Shanghai 201422, China Abstract: Glycyrrhizic acid is hydrolyzed to glycyrrhetic acid in vivo, so glycyrrhizic acid is a prodrug of glycyrrhetic acid. Chemical structure of glycyrrhetic acid is similar to steroid hormone. Glycyrrhetic acid and glycyrrhizic acid are the inhibitors of enzymes (especially 11β-hydroxy-steroid dehydrogenase type 2) in steroid hormone metabolism, therefore they can enhance effects of inactivation endogenic and exogenic corticosteroids. Glycyrrhetic acid and glycyrrhizic acid, as ligands, can combine with corticoid receptor, and show glucocorticoid-like and mineralocorticoid-like effects. Mineralocorticoid-like effect induced by long-term application of licorice or glycyrrhizic acid derivatives can be used for treatment of Addison’s disease. But, for the treatment of other diseases , this effect may become the side effect (major manifestations: pseudoaldosteronism or hypertension), the incidence was more than 50% of their all adverse reactions, and their mechanisms of pseudoaldosteronism or hypertension were discussed in this paper. Key words: glycyrrhizic acid; glycyrrhetic acid; mineralocorticoid-like effect; pseudoaldosteronism; hypertension 甘草酸（glycyrrhizic acid