Ergun Pelin, Kipcak Sezgi, Gorgulu Volkan, Doganavsargil Basak, Bor Serhat
Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, WI, 53226, USA.
Ege Reflux Study Group, Division of Gastroenterology, Faculty of Medicine, Ege University, Izmir, Turkey.
Dig Dis Sci. 2025 Apr 16. doi: 10.1007/s10620-025-08951-x.
Patients undergoing laparoscopic anti-reflux surgery (LARS) often experience improved quality of life and reduced gastroesophageal reflux disease (GERD) symptoms. This study aimed to assess the impact of LARS on epithelial remodeling and repair in the esophageal mucosa.
Upper gastrointestinal (GI) endoscopy was performed once on healthy controls (HC) and twice on GERD patients before and approximately 6 month after surgery, with esophageal biopsies collected. The expressions of E-cadherin (ECAD), Occludin (OCLN), Claudin 1 (CLDN1), Claudin 4 (CLDN4), Zonula Occludens -1 (ZO-1), and ZO-2 were analyzed in the biopsies, and dilated intercellular spaces (DIS) were examined under light microscopy.
The study included 22 GERD patients who were underwent for LARS, and 20 HCs. All patients had pathological reflux episodes. In the Post-LARS group, TEER increased significantly compared to Pre-LARS and HC (p < 0.05), while mucosal permeability decreased (p < 0.05). A significant negative correlation was found between TEER and permeability (p = 0.0002). DIS remained dilated in both Pre- and Post-LARS patients compared to HC (p < 0.05). Gene expression analysis revealed significant increases in ZO-1, OCLN, and ZO-2 Post-LARS (p < 0.05).
LARS improves mucosal integrity by enhancing TEER and reducing permeability in GERD patients, although DIS remains unchanged. The upregulation of tight junction genes such as ZO-1 and OCLN Post-LARS suggests that surgical intervention may support epithelial barrier restoration. DIS remains dilated after LARS; this might be reason that it is not an early marker in GERD pathogenesis. These findings enhance our understanding of GERD nature and may inform future target therapeutic strategies.
接受腹腔镜抗反流手术（LARS）的患者通常生活质量得到改善，胃食管反流病（GERD）症状减轻。本研究旨在评估LARS对食管黏膜上皮重塑和修复的影响。
对健康对照者（HC）进行一次上消化道（GI）内镜检查，对GERD患者在手术前及手术后约6个月各进行一次内镜检查，并采集食管活检组织。分析活检组织中E-钙黏蛋白（ECAD）、闭合蛋白（OCLN）、紧密连接蛋白1（CLDN1）、紧密连接蛋白4（CLDN4）、闭合小环蛋白-1（ZO-1）和闭合小环蛋白-2（ZO-2）的表达，并在光学显微镜下检查细胞间扩张间隙（DIS）。
本研究纳入了22例行LARS的GERD患者和20名HC。所有患者均有病理性反流发作。在LARS术后组，与LARS术前组和HC相比，跨上皮电阻（TEER）显著增加（p<0.05），而黏膜通透性降低（p<0.05）。TEER与通透性之间存在显著负相关（p = 0.0002）。与HC相比，LARS术前和术后患者的DIS均保持扩张（p<0.05）。基因表达分析显示，LARS术后ZO-1、OCLN和ZO-2显著增加（p<0.05）。
LARS通过增强GERD患者的TEER和降低通透性来改善黏膜完整性，尽管DIS保持不变。LARS术后紧密连接基因如ZO-1和OCLN的上调表明手术干预可能有助于上皮屏障的恢复。LARS术后DIS仍保持扩张；这可能是它不是GERD发病机制早期标志物的原因。这些发现加深了我们对GERD本质的理解，并可能为未来的靶向治疗策略提供参考。
