阿司匹林对酸和胆盐诱导的Barrett食管患者食管鳞状细胞NF-κB活化和CDX2表达的影响  

The effect of Aspirin on NF-κB activation and CDX2 expression stimulated by acid and bile salts in esophageal squamous cells of patients with Barrett’s esophagus

作　　者：戴结[1] DAI Jie(Department of Gastroenterology,the PLA Navy Anqing Hospital,Anqing 246003,China)

机构地区：[1]中国人民解放军海军安庆医院消化内科,安徽安庆246003

出　　处：《胃肠病学和肝病学杂志》2020年第3期322-327,共6页Chinese Journal of Gastroenterology and Hepatology

基　　金：北京医卫健康公益基金会资助项目(YWJKJJHKYJJ-A320)。

摘　　要：目的探讨阿司匹林对酸和胆盐诱导的Barrett食管(Barrett’s esophagus,BE)患者食管鳞状细胞NF-κB活化和CDX2表达的影响。方法将合并BE的胃食管反流病(gastroesophageal reflux disease,GERD)患者的食管鳞状细胞(NES-B细胞)和无合并BE的GERD患者的食管鳞状细胞(NES-G细胞)暴露于酸和胆盐中,分别加入和不加入阿司匹林。采用蛋白质印迹法检测细胞内p65、p-p65、p50、IκB、p-IκB的蛋白表达;染色质免疫沉淀法检测p50和p65与CDX2启动子DNA的结合活性;荧光素酶报告基因检测NF-κB/p65的转录活性;免疫荧光技术检测p65蛋白的核转位情况;qRT-PCR法检测CDX2 mRNA的表达。结果NES-B和NES-G细胞在酸和胆盐暴露后均能激活NF-κB,但与NES-G细胞相比,NES-B细胞表现出更高水平的IκB和p65磷酸化,以及更强的NF-κB转录活性。阿司匹林阻断了酸和胆盐诱导的NES-B细胞中IκB磷酸化、p65核转位、CDX2启动子激活和CDX2表达。结论阿司匹林对酸和胆盐诱导的BE患者食管鳞状细胞NF-κB活化和CDX2表达具有抑制作用。Objective To investigate the effect of Aspirin on NF-κB activation and CDX2 expression stimulated by acid and bile salts in esophageal squamous cells of patients with Barrett’s esophagus(BE). Methods The squamous cells from gastroesophageal reflux disease(GERD) patients with BE(NES-B cell) and the squamous cells from GERD patients without BE(NES-G cell) to acid and bile salts were exposed, with and without Aspirin. The expressions of p65, p-p65, p50, IκB and p-IκB in the cells were detected by Western blotting. The binding activity of p50 and p65 to CDX2 promoter DNA was detected by chromatin immunoprecipitation. The NF-κB/p65 transcriptional activity was detected by luciferase reporter gene. The nuclear translocation of p65 protein was detected by immunofluorescence technology. The expression of CDX2 mRNA was detected by qRT-PCR.Results Both NES-B and NES-G cell activated NF-κB after acid and bile salts exposure, but NES-B cell exhibited higher levels of phosphorylated IκB and p65, and greater NF-κB transcriptional activity than NES-G cell. Aspirin blocked IκB phosphorylation, p65 nuclear translocation, CDX2 promoter activation and CDX2 expression induced by acid and bile salts in NES-B cells.Conclusion Aspirin prevents NF-κB activation and CDX2 expression stimulated by acid and bile salts in esophageal squamous cells of patients with BE.

关 键 词：阿司匹林 BARRETT食管 NF-ΚB CDX2 

分 类 号：R571[医药卫生—消化系统]