Ntimbane Thierry, Comte Blandine, Mailhot Geneviève, Berthiaume Yves, Poitout Vincent, Prentki Marc, Rabasa-Lhoret Rémi, Levy Emile
Research Centre, CHU Sainte-Justine, Université de Montréal, Montréal, Québec, Canada.
Clin Biochem Rev. 2009 Nov;30(4):153-77.
Cystic fibrosis (CF) represents the most common lethal autosomal recessive disorder in the Caucasian population. It is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, resulting in abnormal Na(+) and Cl(-) transport in several tissues. Its main clinical manifestations include bronchopulmonary infections along with gastrointestinal and nutritional disorders. Intense and recurrent inflammation ultimately leads to an overabundance of activated neutrophils and macrophages that contribute to free radical generation. Furthermore, CFTR defects directly affect glutathione transport and homeostasis, while intestinal fat malabsorption limits uptake of endogenous antioxidant vitamins. Collectively, these abnormal events disturb the balance between pro- and anti-oxidants and promote oxidative stress, which may play a significant role in CF-related diabetes (CFRD), a severe complication associated with a drastic increase of morbidity and mortality. This review will focus on the involvement of oxidative stress in CF pathology, especially its role in the occurrence of CFRD. The multiple abnormalities in the oxidant/antioxidant balance could be a potential target for a new therapeutic approach.
囊性纤维化（CF）是白种人群中最常见的致死性常染色体隐性疾病。它由囊性纤维化跨膜传导调节因子（CFTR）基因突变引起，导致多个组织中钠（Na⁺）和氯（Cl⁻）转运异常。其主要临床表现包括支气管肺部感染以及胃肠道和营养紊乱。强烈且反复的炎症最终导致大量活化的中性粒细胞和巨噬细胞产生，进而促使自由基生成。此外，CFTR缺陷直接影响谷胱甘肽转运和内环境稳定，而肠道脂肪吸收不良限制了内源性抗氧化维生素的摄取。总体而言，这些异常事件扰乱了抗氧化剂和促氧化剂之间的平衡，促进了氧化应激，氧化应激可能在与CF相关的糖尿病（CFRD）中起重要作用，CFRD是一种严重并发症，与发病率和死亡率的急剧上升相关。本综述将聚焦氧化应激在CF病理中的作用，尤其是其在CFRD发生中的作用。氧化剂/抗氧化剂平衡的多种异常可能是新治疗方法的潜在靶点。
