SYSTEMIC DEFICIENCY OF GLUTATHIONE IN CYSTIC-FIBROSIS
SYSTEMIC DEFICIENCY OF GLUTATHIONE IN CYSTIC-FIBROSIS
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DOI：
10.1152/jappl.1993.75.6.2419
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发表时间：
1993-12-01
影响因子：
3.3
通讯作者：
CRYSTAL, RG
中科院分区：
文献类型：
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作者：
ROUM, JH;BUHL, R;CRYSTAL, RG
囊性纤维化是一种以囊性纤维化跨膜调节基因突变为特征的疾病，以慢性炎症为特征，导致呼吸道上皮进行性损害、支气管扩张和慢性阻塞性肺疾病。导致呼吸道紊乱的一个过程是呼吸道上皮表面炎性细胞释放的氧化剂的长期负担。在此背景下，我们推测与正常人相比，CF患者呼吸道上皮衬里液(ELF)中的谷胱甘肽可能被氧化和/或减少。青年CF患者(n=21)和正常人(n=25)的ELF经支气管肺泡灌洗后恢复，显示CF患者ELF明显以中性粒细胞为主的炎症反应。正如预测的那样，CF患者的ELF的特征是谷胱甘肽缺乏(P<；0.001)，但这是由于还原型谷胱甘肽(P<；0.001)减少而继发的，因为氧化谷胱甘肽的ELF水平没有差异(P>；0.2)。出乎意料的是，血浆中还原型谷胱甘肽也明显缺乏(P<；0.02)；即在CF患者的ELF中观察到的谷胱甘肽“缺乏”不仅限于炎症部位，而且是全身性的。虽然这种全身性细胞外谷胱甘肽缺乏的病因尚不清楚，但在考虑治疗这种疾病伴随的和毁灭性的肺部病理时，这一点很重要。
Cystic fibrosis (CF), a disorder characterized by mutations of the CF transmembrane regulator gene, is characterized in the lung by chronic inflammation, leading to progressive damage to the airway epithelium, bronchiectasis, and chronic obstructive lung disease. One process contributing to the airway derangement is the chronic burden of oxidants released by inflammatory cells on the respiratory epithelial surface. With this background, we hypothesized that glutathione in respiratory epithelial lining fluid (ELF) in CF patients might be oxidized and/or diminished in amount compared with that in normal subjects. Recovery of ELF by bronchoalveolar lavage from young adults with CF (n = 21) and normal subjects (n = 25) demonstrated marked neutrophil-dominated inflammation in ELF in CF patients. As predicted, ELF in CF patients was characterized by a deficiency of glutathione (P < 0.001), but this was secondary to a reduction in reduced glutathione (P < 0.001), inasmuch as there were no differences in ELF levels of oxidized glutathione (P > 0.2). Unexpectedly, there was also a marked deficiency of reduced glutathione in plasma (P < 0.02); i.e., the glutathione ''deficiency'' observed in ELF in CF patients is not limited to the site of the inflammation but is systemic. Although the etiology of this generalized deficiency of extracellular glutathione is unknown, it is important in considering options for treating the concomitant and devastating lung pathology in this disorder.