十二指肠食管反流对p53基因及其表达的影响

Mutation and expression of p53 gene in esophaged mucosa under duodenoesophageal reflux

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 。

Objective To evaluate the influence of duodenoesophageal reflux to mutations or to mRNA and proteinic expression of p53 gene.Methods\ The model of reflux esophagitis and esophageal neoplasm induced by duodenoesophageal reflux were made by operation.The proteinic and mRNA expression of p53 were measured by immunohistochemical studies and hybridization in situ.DNA was extracted and PCR amplification for 5,6,7,8 exon of p53 followed by SSCP and AgNO 3 staining were used to detect mutation of p53 gene.Results\ The expressions of p53 mRNA and protein in reflux group were significantly more than those in C group,and increased with time.No loss of p53 gene was found in two groups.In reflux group,the mutation rates of p53 mutation were higher with time.It(31 6%)was significantly more than that of C group(15 4%)at 40 week.Conclusion\ Duodenoesophageal reflux may increase the mRNA and proteinic expressions of p53 gene and promote mutation in p53 gene in esophageal mucosa.Those may be one of the mechanisms of esophagitis and esophageal neoplasm leading by reflux.