肥大细胞和蛋白酶激活受体-2表达在胃食管反流病中的意义

摘要

Background: Previous studies demonstrated that mast cell ( MC) degranulation and release of inflammatory mediators evoked by intraluminal acid/bile exposure and the protease-activated receptor-2 ( PAR-2) -associated pathways might be involved in the pathogenesis of gastroesophageal reflux disease ( GERD). Evidences suggested that PAR-2 was expressed in human MCs, however, there are very few studies focusing on the correlation of MCs with PAR-2 in GERD. Aims: To investigate the MCs number, its correlation with PAR-2 expression and their significance in esophageal epithelium of patients with GERD. Methods:Sixty-two GERD patients, including 30 erosive esophagitis (EE) and 32 nonerosive reflux disease (NERD) , and 20 normal control subjects were enrolled in this study. Immunohistochemistry was used to determine the MCs number and PAR-2 expression in esophageal epithelium. Results:Number of tryptase-positive MCs and expression intensity of PAR-2 were significantly higher in EE and NERD groups than in normal control group ( P < 0. 01 ) , and no statistically significant difference was found between EE group and NERD group. MCs number was positively correlated with immunohistochemical score of PAR-2 in both EE and NERD groups (r = 0. 875, P < 0. 01; r = 0. 884, P <0.01). Conclusions: Expression of PAR-2 is up-regulated and consistent with the increase of MCs number in esophageal epithelium of patients with GERD. It is presumed that the activation of PAR-2 on MCs may induce MCs degranulation, and subsequently the tryptase released by MCs cleaves and activates PAR-2 on MCs. The interaction between MCs and PAR-2 may partially explain the pathogenesis of GERD.%背景:既往研究显示食管黏膜暴露于酸或胆汁引起的肥大细胞(MC)脱颗粒释放炎症介质以及蛋白酶激活受体-2(PAR-2)相关通路参与了胃食管反流病(GERD)的发病机制.人MC上可能存在PAR-2,但尚未见两者在GERD中关系的报道.目的:研究GERD患者食管黏膜上皮中的MC数量和PAR-2表达情况以及其间的相关性,明确两者在GERD发病中的意义.方法:以免疫组化方法检测30例糜烂性食管炎(EE)、32例非糜烂性反流病(NERD)以及20例正常对照者食管黏膜上皮中的MC数量和PAR-2表达.结果:EE组和NERD组类胰蛋白酶阳性MC数量和PAR-2表达强度均明显高于正常对照组,差异有统计学意义(P＜0.01),EE组与NERD组间差异无统计学意义.EE组和NERD组中的MC数量均与PAR-2免疫组化评分呈正相关(r=0.875,P＜0.01;r=0.884,P＜0.01).结论:GERD患者食管黏膜上皮中的MC数量增多、PAR-2表达上调且两者呈正相关.推测MC表面的PAR-2活化可激活MC脱颗粒,而MC释放的类胰蛋白酶又可激活PAR-2,两者共同参与了GERD的发病机制.