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目的 研究十二指肠液食管反流对食管粘膜中 p5 3基因的突变及表达水平的影响。方法 制作十二指肠食管反流导致反流性食管炎、食管癌的动物模型 ,用原位杂交和免疫组化法分别检测反流不同时间食管上皮 p5 3基因的 m RNA和蛋白表达 ;进行基因组 DNA抽提 ,用 PCR- SSCP法检测食管组织的 p5 3基因突变情况。结果 反流组食管组织中 p5 3基因的蛋白表达和 m RNA表达均显著高于对照组 ,并随病程延长而明显增强。两组均未见 p5 3基因缺失 ,反流组 p5 3突变率随时间延长而增加 ,4 0周时突变率 (31.6 % )显著高于对照组 (15 .4 % )。结论 十二指肠食管反流可在 m RNA及蛋白水平改变食管上皮 p5 3基因的表达 ,并增加 p5 3基因的突变率 ,这可能与其引起反流性食管炎及食管癌等并发症有关
Objective To study the effect of duodenal esophageal reflux on p5 3 gene mutation and expression in esophageal mucosa. Methods The animal models of reflux esophagitis and esophageal cancer caused by duodenal esophageal reflux were made. The expression of m RNA and protein of esophageal epithelial p5 3 gene was detected by in situ hybridization and immunohistochemistry. Genomic DNA extraction was used to detect the mutation of p5 3 gene in esophageal tissue by PCR-SSCP. Results The protein expression and m RNA expression of p5 3 in esophageal tissues of reflux group were significantly higher than those of control group, and were significantly increased with the prolongation of the disease duration. The deletion of p5 3 gene was not observed in both groups. The mutation rate of p5 3 in reflux group increased with time, and the mutation rate (31.6%) at 40 weeks was significantly higher than that of control group (15.4%). Conclusions Duodenal esophageal reflux can change the expression of p5 3 gene in esophageal epithelium and increase the mutation rate of p5 3 gene in m RNA and protein levels, which may be related to the complications such as reflux esophagitis and esophageal cancer