Ballard Stephen T, Parker James C, Hamm Charles R
Department of Physiology, MSB 3074, University of South Alabama, Mobile, AL 36688, USA.
Am J Respir Cell Mol Biol. 2006 Apr;34(4):500-4. doi: 10.1165/rcmb.2005-0214OC. Epub 2005 Dec 15.
Severe impairment of mucociliary transport (MCT) is a hallmark of cystic fibrosis (CF) lung disease. Recent studies demonstrate that pharmacologic inhibition of anion and liquid secretion in pig tracheas models the MCT defect in CF through depletion of the periciliary fluid component of airway surface liquid. In the present study, the effectiveness of various aqueous instillates on rehydration of the airway surface and restoration of MCT was assessed in this model. Excised porcine tracheas were mounted in a chamber that permitted simultaneous measurement of MCT and adventitial exposure of the airways to Krebs solution. When anion and liquid secretion were inhibited by treatment with bumetanide and dimethylamiloride, MCT was greatly reduced. Luminal instillation of aqueous solutions containing surface-active substances (1% Tween80 or calfactant) transiently restored MCT to high rates in nearly all tissues. Mucosal treatment with only Krebs solution or hypertonic saline restored MCT in only one half of the tracheas. We conclude that aqueous salt solutions alone can hydrate airway surfaces and restore MCT in some tissues, but surface-active substances may provide additional benefit in restoring MCT in this model of mucociliary stasis. We speculate that administration of surface-active substances, by aerosol or lavage, might help to restore MCT in the airways of patients with CF.
黏液纤毛转运(MCT)严重受损是囊性纤维化(CF)肺部疾病的一个标志。最近的研究表明,在猪气管模型中,对阴离子和液体分泌的药物抑制通过消耗气道表面液体的纤毛周围液体成分来模拟CF中的MCT缺陷。在本研究中,在该模型中评估了各种水性滴注液对气道表面补液和MCT恢复的有效性。将切除的猪气管安装在一个腔室中,该腔室允许同时测量MCT以及气道对外膜暴露于Krebs溶液的情况。当用布美他尼和二甲基amiloride处理抑制阴离子和液体分泌时,MCT大大降低。向管腔内滴注含有表面活性物质(1%吐温80或钙表面活性剂)的水溶液可使几乎所有组织中的MCT暂时恢复到高速率。仅用Krebs溶液或高渗盐水进行黏膜处理仅能使一半的气管恢复MCT。我们得出结论,仅水性盐溶液就可以使气道表面水化并在某些组织中恢复MCT,但表面活性物质在这个黏液纤毛停滞模型中恢复MCT方面可能会提供额外的益处。我们推测,通过气雾剂或灌洗给予表面活性物质可能有助于恢复CF患者气道中的MCT。