囊性纤维化：太多NaCl，太少HCO_3^-(英文)

Too much salt,too little soda:cystic fibrosis

胰腺囊性纤维化(cystic fibrosis,CF)是一种单基因缺陷导致的致死性遗传疾病,在高加索人种中广泛分布。这种疾病在其它人种的发生率非常低,但据报道大部分人种中发现有该基因的突变。本文对CF发生的分子和病理生理学基本概念进行阐述。首先,阐述了CF的病理学和遗传特征,其基因产物囊性纤维化跨膜电导调节体(cystic fibrosis transmembrane con- ductance regulator,CFTR)的分子结构、特征、功能和调控。其次,由于突变的主要表现是电解质转运失调,其病理学效应和机制在两个典型受累器官中得到了很好的阐明,一个是汗腺,其病理发生是由于分泌过多NaCl,另一个是胰腺,其病理发生是由于分泌太少HCO_3^-。然而,CF的发病率和死亡率主要来自难治性呼吸道感染,其发生机制存存争议,我们推断可能的机制为阴离子转运失调导致CF肺部慢性感染。

Cystic fibrosis （CF） of the pancreas is the most widely accepted name of the most common fatal inherited single gene defect disease among Caucasians. Its incidence among other races is thought to be significantly less, but mutations in the gene have been reported in most, if not all, major populations. This review is intended to give general concepts of the molecular as well as physiological basis of the pathology that develops in the disease. First, an overview of the organ pathology and genetics is presented, followed by the molecular structure of the gene product （cystic fibrosis transmembrane conductance regulator, CFTR）, its properties, functions, and controls as currently understood. Second, since mutations appear to be expressed primarily as a defect in electrolyte transport, effects and mechanisms of pathology are presented for two characteristically affected organs where the etiology is best described： the sweat gland, which excretes far too much NaCl （＂salt＂） and the pancreas, which excretes far too little HCO3 （＂soda＂）. Unfortunately, morbidity and mortality in CF develop principally from refractory airway infections, the basis of which remains controversial. Consequently, we conclude by considering possible mechanisms by which defects in anion transport might predispose the CF lung to chronic infections.