Ylitalo Riitta, Thibeault Susan L
Department of Otolaryngology-Head and Neck Surgery, Karolinska Institute, Stockholm, Sweden.
Ann Otol Rhinol Laryngol. 2006 Oct;115(10):775-83. doi: 10.1177/000348940611501011.
Acid reflux is damaging to the laryngeal mucosa; however, the significance of the duration of reflux episodes has not been evaluated. The purpose of this study was to determine whether varying the exposure times at low pH with or without pepsin alters gene expression in laryngeal fibroblasts.
Human false vocal fold and postcricoidal cultures were exposed to pH 4 or pH 5 media with and without pepsin for 10, 30, 60, and 240 seconds. Using a real-time polymerase chain reaction, we determined the messenger RNA expression of TGFbeta-1, VEGF, FGF-2, EGR-1, ATF-3, CTGF, MMP-1, MMP-2, and decorin.
Molecular responses were initiated at pH 5. Postcricoidal fibroblasts were more sensitive than false vocal fold fibroblasts to the presence of pepsin. Changes in transcript levels were dependent on acid exposure time, and the most significant changes were measured during the first 60 seconds after exposure.
Time of exposure to acid and pepsin needs to be taken into consideration when determining limit of pathology in pharyngeal reflux. Genes are identified that are induced by low pH and that may be of potential importance in the pathogenesis of reflux laryngitis.
胃酸反流会损害喉黏膜；然而，反流发作持续时间的意义尚未得到评估。本研究的目的是确定在有或没有胃蛋白酶的情况下，改变低pH值下的暴露时间是否会改变喉成纤维细胞中的基因表达。
将人假声带和环状软骨后组织培养物暴露于pH值为4或5的含或不含胃蛋白酶的培养基中10、30、60和240秒。使用实时聚合酶链反应，我们测定了转化生长因子β-1（TGFβ-1）、血管内皮生长因子（VEGF）、成纤维细胞生长因子-2（FGF-2）、早期生长反应蛋白-1（EGR-1）、活化转录因子-3（ATF-3）、结缔组织生长因子（CTGF）、基质金属蛋白酶-1（MMP-1）、基质金属蛋白酶-2（MMP-2）和核心蛋白聚糖的信使核糖核酸表达。
在pH值为5时开始出现分子反应。环状软骨后成纤维细胞比假声带成纤维细胞对胃蛋白酶的存在更敏感。转录水平的变化取决于酸暴露时间，并且在暴露后的前60秒内测量到最显著的变化。
在确定咽反流的病理限度时，需要考虑酸和胃蛋白酶的暴露时间。已鉴定出由低pH值诱导且可能在反流性喉炎发病机制中具有潜在重要性的基因。
