【摘要】 目的探讨内皮素1(endothelin-1,ET-1)及其受体在反流性食管炎及Barrett食管(Barrett esophagus,BE)中的表达及其意义。方法用免疫组化法及实时定量PCR方法检测内镜活检标本:正常食管上皮20例,反流性食管炎22例,长段BE14例中ET-1及其受体ET(A)R、ET(B)R的表达。结果反流性食管炎中ET-1及ET(A)RmRNA水平均显著高于正常食管上皮(3.25±1.78vs.1.10±0.71,P=0.000;2.13±1.06vs.1.12±0.64,P=0.001)。BE近侧端的ET-1mRNA水平显著高于BE远侧端(3.03±1.83vs.1.16±0.70,P=0.004)及正常食管上皮(P=0.002)。BE两端的ET(A)R及ET(B)RmRNA水平相比差异无统计学意义(P>0.05)。免疫组化法显示,ET-1在反流性食管炎中的阳性表达(51.18±30.14)显著高于正常食管上皮(21.10±18.17,P=0.000)及BE远侧端(28.02±24.92,P=0.022),近侧端BE的阳性表达(50.07±25.88)显著高于BE远侧端(P=0.030)及正常食管上皮(P=0.001)。在反流性食管炎,轻、中、重度炎症评级的ET-1表达分值分别为36.08±27.84,65.86±11.82,98.00±8.49,呈阶梯式升高,组间差异有统计学意义(P=0.003)。ET(A)R及ET(B)R在炎症及非炎症组织中表达均较弱,各组间差异均无统计学意义(P>0.05)。结论 ET-1及ET(A)R在反流性食管炎中表达增加可能与炎症有关,ET-1可能在BE的形成过程中起作用。更多还原

【Abstract】 Objective To examine the expression of endothelin-1(ET-1)and its receptors in human reflux esophagitis and Barrett esophagus.Methods Endoscopic biopsies of normal squamous epithelium(NSE)(n=20),reflux esophagitis(RE)(n=22),and long segment Barrett esophagus(BE)(n=14)were obtained.The segmental degree of endoscopic and histopathological inflammation was graded,and immunohistochemistry and real-time quantitative polymerase chain reaction were used to determine the expression of ET-1 and its receptors:ET(A)R and ET(B)R.Results ET-1 and ET(A)R mRNA levels were higher in RE than in normal squamous epithelium(3.25±1.78 vs.1.10±0.71,P=0.000;2.13±1.06 vs.1.12±0.64,P=0.001,respectively).In BE,relative ET-1 mRNA levels in the proximal segment were higher than in the distal segment(3.03±1.83 vs.1.16±0.70,P=0.004)and in normal esophageal epithelium(P=0.002).There was no significantly difference of ET(A)R mRNA levels between the proximal segment and the distal segment(1.99±1.28 vs.1.14±0.67,P=0.072).ET(B)R mRNA expression was unaltered between the groups.Furthermore,immunohistochemistry demonstrated that ET-1 expression increased significantly in RE(51.18±30.14)compared to those in normal squamous epithelium(21.10±18.17,P=0.000)and in distal BE segment(28.02±24.92,P=0.022).There were more ET-1 positive cells in proximal BE segment(50.07±25.88)than in distal BE segment(P=0.030)and in normal squamous epithelium(P=0.001).ET-1 expression increased in a stepwise manner with the growing degree of inflammation,and there were significant differences between mild,moderate,and marked degree esophagitis(36.08±27.84,65.86±11.82,98.00±8.49,P=0.003).However,expression of receptors remained unchanged.Conclusions This study demonstrates that overexpression of ET-1 and ETAR in esophagitis may be related to the inflammatory process.ET-1 may play a significant role in the progression of Barrett metaplasia.更多还原