食管反流促进肿瘤发生与抑癌基因mRNA表达的相关性

ASSOCIATION BETWEEN DIFFERENT REFLUX IN ESOPHAGUS AND mRNA EXPRESSIONS OF p53,p16 AND p21 DURING ESOPHAGEAL TUMORIGENESIS OF RATS

为研究胃十二指肠食管反流的大鼠诱癌过程中食管组织内p5 3、p16、p2 1等抑癌基因的mRNA表达 ,制作 3种食管反流动物模型及对照组 ,术后均注射致癌剂 ,用原位杂交法检测术后 2 0、2 6周时食管组织中p5 3、p16、p2 1基因的mRNA表达。结果显示 ,各反流组食管上皮中p5 3的mRNA表达均较对照组显著增强 ,其中十二指肠食管反流组 (D组 )、十二指肠胃食管反流组 (DG组 )的表达较胃食管反流组 (G组)更强 ,D组与DG组结果相似 ;D、DG组的p16、p2 1基因mRNA表达较C组减弱 ,而G组与C组相比差异无显著性意义。提示胃液及十二指肠内容物反流可改变抑癌基因在转录水平的表达 ,促进大鼠食管肿瘤的发生 。

The aim of this study was to investigate the mRNA expressions of p53,p16 and p21 in esophagus under duodenoesophageal reflux and gastroesophageal reflux and to discuss the mechanism of reflux leading to esophageal tumorigenesis. Three kinds of model groups [gastroesophageal reflux(G), duodenoesophageal reflux(D) and duodenogastroesophageal reflux(DG)] and a control group(C) were made by operations. All rats were given carcinogen and the mRNA expressions of p53, p16 and p21 were measured by in situ hybridization. The expression of p53 mRNA in all reflux groups was significantly more than that in group C, and in groups D and DG was significantly more than that in group G. The expressions of p16 and p21 gene decreased in all reflux groups and were significantly lower than those in group C, but there was no difference between these reflux groups. It is concluded that reflux of both gastric juice and duodenal contents can promote tumourigenesis in esophagus by changing the expressions of neoplasm inhibiting genes.The effect of duodenal contents is stronger than that of gastric juice.