食管诱癌过程中不同反流状态对抑癌基因表达蛋白的影响

目的：研究胃及十二指肠内容物反流对食管组织内抑癌基因表达蛋白的影响，从而探讨不同反流状态下食管肿瘤发生的机制。方法：通过不同手术方式制作单纯胃食管反流（G组）、单纯十二指肠食管反流（D组）、十二指肠胃混合食管反流（DG组）及无反流对照组（C组）动物模型，术后均注射致癌剂甲基戊基亚硝胺（MANA），于26周取食管，用且化法检测组织中P53，P16，P21等基因的蛋白表达，结果：各反流组大鼠食管上皮细胞中突变型P53蛋白的表达均较对照组显著增强，反流组间相比无显著差异，各反流组P16，P21蛋白的表达较对照组减弱（G组P16蛋白表达与C组相比无显著差别），其中D组、DG组的表达较G组更弱，D组与DG组结果相似，突变型P53蛋白折表达与P16，P21蛋白的表达呈负相关（r分别为－0．62及－0．75）,P16蛋白的表达与P21蛋白的表达呈正相关(r=0.54)。结论胃液及十二指肠内容物反流可通过改变抑癌基因的蛋白表达而影响致癌剂甲基戊基亚硝胺诱发大鼠食管肿瘤的作用，其中十二指肠内容物的作用较胃液更强。

Expression of P53, P16 and P21 proteins in esophagus under 3 sorts of esophageal reflux during tumorgenesis in rats

Objective: To investigate the expression of P53,P16 and P21 proteins in esophagus in duodenoesophageal reflux and gastroesophageal reflux. Methods: Four kinds of model: gastroesophageal reflux(G group), duodenoesophageal reflux(D group) and duodenogastroesophageal reflux(DG group), and control group (C group) were obtained by operations.All rats were given carcinogen (methyl n amyl nitrosamine,MANA).Then their esophagi were taken 26 weeks after operation. The expression of P53,P16 and P21 proteins were measured by immunohistochemical study. Results: The expression of mutational P53 protein increased in all reflux groups and were significantly stronger than that in C group.There was no difference between 3 kinds of reflux groups. The expression of P16 and P21 proteins in all reflux groups(except P16 protein in G group) were significantly lower than those in C group,and those in D and DG groups were significantly lower than those in G group. Conclusion: Both gastric juice and duodenal content reflux can promote tumourgenesis of MANA in rats esophagi by changing the expression of neoplasm inhibiting genes.The effect of duodenal content is stronger than gastric juice.It may play an important role in tumourgenesis of gastroesophageal reflux disease.