一氧化氮合酶、环氧合酶-2在不同类型胃食管反流病中的表达及意义

Significance of expression of nitric oxide synthetase and cyclooxygenase-2 in different types of gastroesophageal reflux disease

背景非糜烂性胃食管反流病(non-erosive reflux disease,NERD)、反流性食管炎(reflux esophagitis,RE)、Barrett食管(barrett esophageal,BE)三种类型NERD转化少,独立性较强,临床表现和预后均有一定差异,其中NERD最为常见,但诊断难度最大.报道显示,NOS、COX-2在胃食管反流病(gastroesophageal reflux disease,GERD)呈高表达,但在不同类型GERD方面报道较少,推测一氧化氮合酶(nitric oxide synthetase,NOS)、环氧合酶-2(cyclooxygenase-2,COX-2)对NERD的诊断有一定价值.目的探究NOS、COX-2在不同类型胃食管反流病中的表达及意义.方法前瞻性选取2015-01/2019-12我院内科收治的GERD患者78例作为观察组,按照GERD不同类型分为NERD、RE、及BE 3组;另选取同期在本院门急诊及体检中心进行胃镜检查的26例健康人群作为对照组.比较各组NOS mRNA、COX-2 mRNA表达,并分析两者相关性,以及NOS mRNA、COX-2 mRNA对NERD的诊断作用.结果内镜及组织病理学检查显示,78例GERD患者中,RE组26例、NERD组28例、BE组24例;各组患者在性别年龄等一般资料比较无显著差异(P>0.05),3种不同类型GERD的NOS mRNA[神经元型一氧化氮合酶(neuronal nitric oxide synthase,nNOS)mRNA、诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)mRNA]、COX-2 mRNA表达水平明显高于对照组,且BE组NOS mRNA、COX-2 mRNA表达水平明显高于RE组,RE组NOS mRNA、COX-2 mRNA表达水平明显高于NERD组,差异均有统计学意义(P<0.05).nNOS mRNA、iNOS mRNA与COX-2 mRNA均呈显著正相关(r=0.900、0.897,P<0.05).受试者工作特征曲线分析显示,nNOS mRNA诊断NERD的曲线下面积(area under the curve,AUC)为0.662,iNOS mRNA诊断NERD的AUC为0.671,COX-2 mRNA诊断NERD的AUC为0.613;Z检验AUC发现差异无统计学意义(P>0.05),根据最佳临界值,当nNOS mRNA高于1.505时,其敏感度为65.8%,特异度为89.3%;当iNOS mRNA高于1.795时,其敏感度为63.2%,特异度为100%;当COX-2 mRNA高于1.895时,其敏感度为55.3%,特异度为92.9%.结论NOS、COX-2在不同类型胃食管反流病中均呈高表达,其中在BE患者中表达最高,RE患者中表达次之,NERD患者中表达最少,并且对NERD的诊断有一定参考价值.

BACKGROUND Non-erosive reflux disease(NERD),reflux esophagitis(RE),and Barrett’s esophagus(BE),the three types of gastroesophageal reflux disease(GERD),have strong independence,and there are certain differences in their clinical manifestations and prognosis.NERD is the most common,but its diagnosis is the most difficult.Reports show that nitric oxide synthetase(NOS)and cyclooxygenase-2(COX-2)are highly expressed in GERD,but there are few reports on their expression in different types of GERD.It is speculated that NOS and COX-2 have certain value in the diagnosis of NERD.AIM To explore the significance of expression of NOS and COX-2 in different types of GRED.METHODS From January 2015 to December 2019,78 GERD patients admitted to the Department of Gastroenterology of our hospital were prospectively selected.According to the type of GERD,they were divided into three groups:NERD,RE,and BE.In addition,26 healthy people who underwent gastroscopy at the Physical Examination Center of our hospital during the same period were selected as a control group.The expression levels of NOS mRNA and COX-2 mRNA in each group were compared,and the correlation between them was analyzed.RESULTS Endoscopic and histopathological examinations showed that in 78 GERD patients,there were 26 cases of RE,28 cases of NERD,and 24 cases of BE.There was no significant difference in sex or age among the three groups(P>0.05).The expression levels of NOS mRNA[neuronal nitric oxide synthase(nNOS)mRNA and inducible nitric oxide synthase(iNOS)mRNA]and COX-2 mRNA in the three different types of GERD were significantly higher than those in the control group,and NOS and COX-2 mRNA expression levels in the BE group were significantly higher than those in the control group.The expression levels of NOS mRNA and COX-2 mRNA in the RE group were significantly higher than those in the NERD group(P<0.05).There was a significant positive correlation between nNOS and iNOS and COX-2 mRNA expression(r=0.900,0.897,P<0.05).Receiver operating characteristic curve analysis showed that the areas under the curves of nNOS mRNA,iNOS mRNA,and COX-2 mRNA in diagnosing NERD were 0.662,0.671,and 0.613,respectively,which showed no significant difference(P>0.05).According to the best critical value,when nNOS mRNA expression was higher than 1.505,the sensitivity was 65.8%and the specificity was 89.3%;when iNOS mRNA was higher than 1.795,the sensitivity was 65.8%;when COX-2 mRNA was higher than 1.895,the sensitivity was 55.3%and the specificity was 92.9%.CONCLUSION NOS and COX-2 are highly expressed in different types of GRED,and their expression is the highest in BE,followed by RE and NERD.NOS and COX-2 expression may have appreciated value for the diagnosis of NERD.