Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Am J Gastroenterol. 2013 Apr;108(4):535-43. doi: 10.1038/ajg.2012.469. Epub 2013 Jan 29.
Intact esophageal mucosal integrity is essential to prevent symptoms during gastroesophageal reflux events. Approximately 70% of patients with heartburn have macroscopically normal esophageal mucosa. In patients with heartburn, persistent functional impairment of esophageal mucosal barrier integrity may underlie remaining symptoms. Topical protection of a functionally vulnerable mucosa may be an attractive therapeutic strategy. We aimed to evaluate esophageal mucosal functional integrity in patients with heartburn without esophagitis, and test the feasibility of an alginate-based topical mucosal protection.
Three distal esophageal biopsies were obtained from 22 patients with heartburn symptoms, and 22 control subjects. In mini-Ussing chambers, the change in transepithelial electrical resistance (TER) of biopsies when exposed to neutral, weakly acidic, and acidic solutions was measured. The experiment was repeated in a further 10 patients after pretreatment of biopsies with sodium alginate, viscous control, or liquid control "protectant" solutions.
Biopsy exposure to neutral solution caused no change in TER. Exposure to weakly acidic and acidic solutions caused a greater reduction in TER in patients than in controls (weakly acid -7.2% (95% confidence interval (CI) -9.9 to -4.5) vs. 3.2% (-2.2 to 8.6), P<0.05; acidic -22.8% (-31.4 to 14.1) vs. -9.4% (-17.2 to -1.6), P<0.01). Topical pretreatment with alginate but not with control solutions prevented the acid-induced decrease in TER (-1% (-5.9 to 3.9) vs. -13.5 (-24.1 to -3.0) vs. -13.2 (-21.7 to -4.8), P<0.05).
Esophageal mucosa in patients with heartburn without esophagitis shows distinct vulnerability to acid and weakly acidic exposures. Experiments in vitro suggest that such vulnerable mucosa may be protected by application of an alginate-containing topical solution.
完整的食管黏膜完整性对于预防胃食管反流事件期间的症状至关重要。约 70%的烧心患者的食管黏膜宏观上正常。在烧心患者中,食管黏膜屏障完整性的持续功能障碍可能是残留症状的基础。对功能脆弱的黏膜进行局部保护可能是一种有吸引力的治疗策略。我们旨在评估无食管炎的烧心患者的食管黏膜功能完整性,并测试基于藻酸盐的局部黏膜保护的可行性。
从 22 例烧心症状患者和 22 例对照中获得 3 个远端食管活检。在迷你 Ussing 室中,测量活检在暴露于中性、弱酸性和酸性溶液时跨上皮电阻(TER)的变化。在进一步的 10 例患者中,重复进行实验,在活检预处理后使用藻酸钠、粘性对照或液体对照“保护剂”溶液。
活检暴露于中性溶液不会引起 TER 变化。与对照组相比,活检暴露于弱酸性和酸性溶液会导致患者的 TER 更大幅度下降(弱酸性 -7.2%(95%置信区间(CI)-9.9 至 -4.5)与 3.2%(-2.2 至 8.6),P<0.05;酸性 -22.8%(-31.4 至 14.1)与-9.4%(-17.2 至 -1.6),P<0.01)。藻酸盐而非对照溶液的局部预处理可防止酸诱导的 TER 下降(-1%(-5.9 至 3.9)与-13.5(-24.1 至 -3.0)与-13.2(-21.7 至 -4.8),P<0.05)。
无食管炎的烧心患者的食管黏膜对酸和弱酸性暴露显示出明显的脆弱性。体外实验表明,含有藻酸盐的局部溶液应用可能保护这种脆弱的黏膜。