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首页> 外文期刊>Experimental Physiology >Role of the amiloride-sensitive epithelial Na+ channel in the pathogenesis and as a therapeutic target for cystic fibrosis lung disease.
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Role of the amiloride-sensitive epithelial Na+ channel in the pathogenesis and as a therapeutic target for cystic fibrosis lung disease.

机译：阿米洛利敏感性上皮Na +通道在发病机理中的作用以及作为囊性纤维化肺病的治疗靶标的作用。

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摘要

Increased airway Na(+) absorption mediated by the amiloride-sensitive epithelial Na(+) channel (ENaC) is a basic defect in cystic fibrosis (CF) lung disease. Cystic fibrosis is one of the most common lethal hereditary diseases and is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The CFTR acts as a cAMP-dependent Cl(-) channel and regulator of ENaC, and CFTR dysfunction causes impaired Cl(-) secretion and increased Na(+) absorption in the airways of CF patients. Evidence from in vitro studies suggested that increased Na(+) absorption produces airway surface liquid (ASL) volume depletion and led to the generation of transgenic mice with airway-specific overexpression of ENaC to elucidate the role of this mechanism in the in vivo pathogenesis of lung disease. Studies of the pulmonary phenotype of betaENaC-overexpressing mice demonstrated that increased airway Na(+) absorption caused ASL depletion and reduced mucus transport, producing a CF-like lung disease with airway mucus plugging, chronic airway inflammation and pulmonary mortality. Further, recent pharmacological studies demonstrated that preventive, but not late, inhibition of increased airway Na(+) absorption with the ENaC blocker amiloride reduced morbidity and mortality in this murine model of CF lung disease. These results support a critical role of ENaC in the in vivo pathogenesis of CF lung disease and suggest that amiloride may be an effective preventive therapy for CF patients.
机译：阿米洛利敏感上皮Na（+）通道（ENaC）介导的气道Na（+）吸收增加是囊性纤维化（CF）肺病的基本缺陷。囊性纤维化是最常见的致死性遗传疾病之一，由囊性纤维化跨膜电导调节剂（CFTR）基因突变引起。 CFTR充当依赖cAMP的Cl（-）通道和ENaC的调节剂，CFTR功能障碍导致CF患者气道中Cl（-）分泌受损和Na（+）吸收增加。体外研究的证据表明，Na（+）吸收的增加会导致气道表面液（ASL）的体积消耗，并导致具有气道特异性过表达ENaC的转基因小鼠的产生，以阐明该机制在肝癌的体内发病机理中的作用。肺部疾病。 betaENaC过表达小鼠的肺表型研究表明，气道Na（+）吸收增加会导致ASL耗竭并减少粘液运输，从而产生CF样肺病，并伴有气道粘液堵塞，慢性气道炎症和肺部死亡。此外，最近的药理研究表明，使用CFG鼠模型的ENaC阻断剂阿米洛利可以预防性地（但不晚）抑制气道Na（+）吸收增加，从而降低了发病率和死亡率。这些结果支持ENaC在CF肺病的体内发病机制中的关键作用，并提示阿米洛利可能是CF患者的有效预防方法。

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