Rahman Irfan
Department of Environmental Medicine, Lung Biology and Disease Program, University of Rochester Medical Center, 601 Elmwood Ave, Box 850, Rochester, NY 14642, USA.
Int J Chron Obstruct Pulmon Dis. 2006;1(1):15-29. doi: 10.2147/copd.2006.1.1.15.
Oxidative stress is an important feature in the pathogenesis of COPD. Targeting oxidative stress with antioxidants or boosting the endogenous levels of antioxidants is likely to be beneficial in the treatment of COPD. Antioxidant agents such as thiol molecules (glutathione and mucolytic drugs, such as N-acetyl-L-cysteine and N-acystelyn), dietary polyphenols (curcumin, resveratrol, green tea, catechins/quercetin), erdosteine, and carbocysteine lysine salt, all have been reported to control nuclear factor-kappaB (NF-kappaB) activation, regulation of glutathione biosynthesis genes, chromatin remodeling, and hence inflammatory gene expression. Specific spin traps such as alpha-phenyl-N-tert-butyl nitrone, a catalytic antioxidant (ECSOD mimetic), porphyrins (AEOL 10150 and AEOL 10113), and a superoxide dismutase mimetic M40419 have also been reported to inhibit cigarette smoke-induced inflammatory responses in vivo. Since a variety of oxidants, free radicals, and aldehydes are implicated in the pathogenesis of COPD, it is possible that therapeutic administration of multiple antioxidants will be effective in the treatment of COPD. Various approaches to enhance lung antioxidant capacity and clinical trials of antioxidant compounds in COPD are discussed.
氧化应激是慢性阻塞性肺疾病（COPD）发病机制中的一个重要特征。使用抗氧化剂靶向氧化应激或提高内源性抗氧化剂水平可能对COPD的治疗有益。抗氧化剂如硫醇分子（谷胱甘肽和黏液溶解药物，如N-乙酰-L-半胱氨酸和N-乙酰半胱氨酸）、膳食多酚（姜黄素、白藜芦醇、绿茶、儿茶素/槲皮素）、厄多司坦和半胱氨酸赖氨酸盐，均已报道可控制核因子-κB（NF-κB）的激活、调节谷胱甘肽生物合成基因、染色质重塑，从而调控炎症基因表达。特定的自旋捕捉剂如α-苯基-N-叔丁基硝酮、一种催化抗氧化剂（模拟细胞外超氧化物歧化酶）、卟啉（AEOL 10150和AEOL 10113）以及一种超氧化物歧化酶模拟物M4’0419，也已报道可在体内抑制香烟烟雾诱导的炎症反应。由于多种氧化剂、自由基和醛类参与了COPD的发病机制，因此联合使用多种抗氧化剂进行治疗可能对COPD有效。本文讨论了增强肺抗氧化能力的各种方法以及COPD中抗氧化化合物的临床试验。
