胃食管反流病患者食管上皮Occludin的表达及细胞间隙的改变

Expression of tight junction protein occludin and changes in intercellular space in the esophageal epithelium in patients with gastroesophageal reflux disease

目的:研究胃食管反流病(GERD)患者食管上皮细胞紧密连接蛋白Occludin表达的变化及食管上皮细胞间隙的改变.方法:采用免疫组织化学法检测62例GERD患者[其中反流性食管炎(RE组)患者30例,非糜烂性反流病(NERD组)患者32例]及10例正常对照食管下段上皮的紧密连接蛋白Occludin表达,并在光镜下观察切片并采集图像,采用图像分析系统对每例切片测量100个细胞间隙,进行统计学分析.结果:10例正常对照组Occludin呈正常连续的细胞膜表达,NERD组4例正常表达,28例不同程度异常表达,为细胞膜不完整表达、细胞质表达及表达缺失,30例RE均表达异常;RE组和NERD组Occludin阳性率与正常对照组比较,差异均有显著性(P<0.01),而RE组与NERD组间比较,无显著差异.RE组和NERD组平均细胞间隙与正常对照组比较,均有显著性差异(1.51±0.31μm,1.38±0.26μm vs0.77±0.12μm,均P<0.01),而RE组和NERD组间无显著差异.结论:胃食管反流病患者食管上皮Occludin数量减少、分布异常,导致细胞间隙增宽,影响黏膜上皮屏障的完整性,可能是胃食管反流病的发病机制之一.

AIM：To investigate the distribution and expression of tight junction protein occludin and observe changes in intercellular space in the esophageal epithelium in patients with gastroesophageal reflux disease （GERD）. METHODS：Sixty-two GERD patients （30 cases of reflux esophagitis （RE） and 32 cases of nonerosive reflux disease （NERD） and 10 non-GERD patients were included in the study. Immunohistochemistry was used to examine the distribution and expression of occludin in the esophageal epithelium in these patients. The stainedsections were observed and photographed under light microscopy. The intercellular space in the esophageal epithelium was measured by computer-assisted morphometry. One hundred measurements were performed in each case to calculate the mean intercellular space diameter. RESULTS：Occludin was distributed continuously in the cell membrane in normal esophageal epithelium. Of 32 NERD patients,4 showed normal occludin expression,and 28 showed varying degrees of aberrant occludin expression （e.g.,incomplete membrane expression,cytoplasmic expression and expression loss）. In contrast,all RE patients showed aberrant occludin expression. The rates of aberrant occludin expression in NERD and RE patients were significantly higher than that in non-GERD patients （both P〈0.01）. No significant difference was observed in the rate of aberrant occludin expression between RE and NERD patients （P〈0.05）. The mean intercellular space diameters in NERD and RE patients were signifi cantly higher than that in non-GERD patients （1.38 ± 0.26 μm and 1.51 ± 0.31 μm vs 0.77 ± 0.12 μm,respectively; both P〈0.01）. No signif icant difference was noted in the mean intercellular space diameter between RE and NERD patients （P〈0.05）. CONCLUSION：Occludin shows diminished expression and altered distribution in the esophageal epithelium in patients with gastroesophageal reflux disease. Aberrant expression of occludin may result in dilated intercellular space and impair the integrity of mucosal epithelial barrier,which may partly explain the pathogenesis of GERD.