Borowitz Drucy
University at Buffalo, State University of New York, Buffalo, New York.
Pediatr Pulmonol. 2015 Oct;50 Suppl 40:S24-S30. doi: 10.1002/ppul.23247.
The gene that encodes for the cystic fibrosis transmembrane regulator protein (CFTR) was identified in 1989, yet major pathophysiologic questions remain unanswered. There is emerging evidence that CFTR is a bicarbonate channel, a driver of chloride-bicarbonate exchange and through its action on local pH, a regulator of other ion channels and of proteins that function optimally in a neutral environment. In both the respiratory and gastrointestinal (GI) tracts, bicarbonate drives ionic content and fluid on epithelial surfaces, allows mucins to unfold and become slippery, and contributes to innate immunity. In the GI tract bicarbonate neutralizes gastric acid to support digestion and absorption. When CFTR is dysfunctional, lack of bicarbonate secretion disrupts these normal processes and thus leads directly to the clinical symptoms and signs of CF. This article synthesizes evidence from cell, animal, and human investigations that support these concepts. Bicarbonate secretion does not seem to be the same in all tissues and varies with physiologic demand. Thus, tissue type and whether conditions are baseline or stimulated needs to be taken into account when evaluating the evidence concerning the role of bicarbonate in the pathophysiology of CF as a regulator of local pH. Basic and applied research that focuses on the role of CFTR-mediated bicarbonate secretion helps explain many of the diverse clinical manifestations that are CF.
编码囊性纤维化跨膜调节蛋白（CFTR）的基因于1989年被发现，但主要的病理生理学问题仍未得到解答。越来越多的证据表明，CFTR是一种碳酸氢盐通道，是氯-碳酸氢盐交换的驱动因素，并通过其对局部pH的作用，调节其他离子通道以及在中性环境中最佳发挥功能的蛋白质。在呼吸道和胃肠道中，碳酸氢盐驱动上皮表面的离子成分和液体，使粘蛋白展开并变得光滑，并有助于先天免疫。在胃肠道中，碳酸氢盐中和胃酸以支持消化和吸收。当CFTR功能失调时，碳酸氢盐分泌不足会破坏这些正常过程，从而直接导致CF的临床症状和体征。本文综合了来自细胞、动物和人体研究的证据，支持这些概念。碳酸氢盐分泌在所有组织中似乎并不相同，并随生理需求而变化。因此，在评估关于碳酸氢盐作为局部pH调节剂在CF病理生理学中的作用的证据时，需要考虑组织类型以及条件是基线还是受刺激状态。专注于CFTR介导的碳酸氢盐分泌作用的基础和应用研究有助于解释CF的许多不同临床表现。
