不同亚型胃食管反流病食管黏膜下层炎症因子变化特点研究

Expression and clinical significance of interleukins in different subtypes of gastroesophageal reflux disease

目的分析3种亚型胃食管反流病患者与对照组食管黏膜的组织变化和局部IL-4、IL-6表达,探讨Th2型炎症因子在胃食管反流病发生发展中的作用。方法选取2016年12月至2017年12月新疆维吾尔自治区人民医院69例患者临床资料,根据Gerd Q评分和内镜结果将所有入选研究者分为Barrett食管(BE)、糜烂性食管炎(EE)、非糜烂性反流病(NERD)和对照4组,利用食管24 h pH监测法评价胃食管反流病(GERD)患者食管酸暴露及反流特点;通过食管组织HE染色进行组织病理学评分,使用免疫组化法和酶联免疫吸附剂测定法检测食管局部及血清中IL-4、IL-6表达情况。结果食管24 h pH监测结果中,3亚组间DeMeester指数、弱酸反流次数、反流总事件数比较,差异均无统计学意义(P均>0.05),NERD组酸反流次数较其余2组低,差异有统计学意义(P均<0.05);4组样本食管黏膜组织病理学评分中发现,BE组、EE组与其余2组相比均明显升高,差异有统计学意义(P均<0.05),BE组与EE组评分之间亦有显著差异(P<0.05),NERD组与对照组间差异不明显;IL-4在4组食管标本中均有不同程度表达,但4组间IL-4阳性率的比较并无显著差异(P均>0.05);IL-6在NERD组和对照组表达量较低甚至不表达,EE组IL-6阳性率明显高于对照组(P<0.05),但与NERD组间无显著差异,BE组阳性率与对照组和NERD组之间均有明显差异(P均<0.05)。结论 GERD食管黏膜上皮组织学炎症等级随食管炎的恶化而升高,其中NERD的食管组织学已出现炎性化趋势,但尚不足以与正常食管区别;IL-4在不同亚型GERD食管黏膜组织中的表达差异不及IL-6显著。

Objective To investigate the expression of IL-4, IL-6 in Barrett esophagus (BE), erosive esophagitis (EE) and nonerosive reflux disease (NERD) and the role they played in gastroesophageal reflux disease (GERD). Methods Patients of BE, EE, NERD and control group were carefully selected according to the results of GERD Questionnaire and endoscopy. 24-hour ambulatory esophageal pH monitoring was used to estimate the GERD patients' esophageal acid exposure. Esophageal biopsies taken at endoscopy in all four groups were observed in microscopy for histopathology, and tested by immunohistochemistry (IHC) staining for cytokines IL-4 and IL-6. Results In the 24 h pH monitorin DeMeester score showed no significant differences in three GERD subtype groups (P>0.05), neither were the results of 4<pH<7 (weak acid) reflux event nor the total reflux event. The event of pH<4 (acid) reflux was significantly lower in NERD group (P<0.05). In the comparison of the four groups including the control of the esophageal mucosal histopathological grading, BE and EE had significantly higher inflammatory score (P<0.05);and the difference between NERD group and the control was not significant. Detecting the IL-4 expression in specimens of esophageal, there was no considerable difference between the four groups (P> 0.05). The expression of IL-6 in the esophagus of NERD group and the control was significantly low or not even detected, but was markedly higher in the EE group than that in the control group (P<0.05). Conclusions Histological inflammation level of GERD esophageal mucosal epithelium is increased with the deterioration of esophagitis. Rather than IL-4, IL-6 is more significantly expressed in esophagus between different subtypes of GERD.