Patterson C E, Rhoades R A
Department of Physiology and Biophysics, Indiana University School of Medicine, Indianapolis 46223.
Exp Lung Res. 1988;14 Suppl:1005-19. doi: 10.3109/01902148809064189.
Recently there has been a great deal of interest in exploring possible ways to protect the lung from oxidant damage. Since sulfhydryl compounds are among the most important endogenous antioxidants, their therapeutic use has been proposed. Glutathione (GSH), the main intracellular nonprotein sulfhydryl, plays an important role in the maintenance of cellular proteins and lipids in their functional state. With oxidant stress, GSH acts to protect cell constituents as evidenced by increased turnover to GSSG, formation of mixed disulfides with proteins, utilization of NADPH, and utilization of glucose in the pentose pathway. When GSH is experimentally lowered (e.g., by protein deficiency or with diethylmaleate) the toxic effects of oxidant stress are exacerbated as evidenced by increased membrane and cell damage, pulmonary edema, and mortality. Several recent investigations have shown that sulfhydryl reagents (particularly N-acetyl cysteine, a cell-permeable GSH precursor) can provide significant protection against certain pulmonary toxins. N-acetyl cysteine reduced the lethal effects of 100% O2 in rats by 65%. Therefore, the therapeutic potential of sulfhydryl reagents in the treatment and prevention of oxidant injury and the mechanisms involved are an important direction for lung research.
最近，人们对探索保护肺部免受氧化损伤的可能方法产生了浓厚兴趣。由于巯基化合物是最重要的内源性抗氧化剂之一，因此有人提出了它们的治疗用途。谷胱甘肽（GSH）是主要的细胞内非蛋白质巯基，在维持细胞蛋白质和脂质的功能状态方面发挥着重要作用。在氧化应激情况下，GSH通过增加向氧化型谷胱甘肽（GSSG）的周转、与蛋白质形成混合二硫键、利用烟酰胺腺嘌呤二核苷酸磷酸（NADPH）以及在戊糖途径中利用葡萄糖来保护细胞成分。当通过实验降低GSH水平时（例如，通过蛋白质缺乏或使用马来酸二乙酯），氧化应激的毒性作用会加剧，表现为膜和细胞损伤增加、肺水肿和死亡率上升。最近的几项研究表明，巯基试剂（特别是N-乙酰半胱氨酸，一种可透过细胞的GSH前体）可以对某些肺部毒素提供显著保护。N-乙酰半胱氨酸使大鼠在100%氧气环境中的致死效应降低了65%。因此，巯基试剂在治疗和预防氧化损伤方面的治疗潜力及其涉及的机制是肺部研究的一个重要方向。
