肿瘤诱发过程中反流对食管上皮细胞增殖及DNA倍体的影响

为研究不同类型反流对食管上皮细胞增殖及DNA倍体的影响在食管肿瘤诱发过程中的作用。制作单纯胃食管反流（G组），单纯十二指肠食管反流（D组）、胃十二指肠混合液食管反流（DG组）及无反流对照（C组）大鼠模型。于术后4周开始腹腔内注射食管致癌剂甲基戊基亚硝胺（MANA），5mg/kg，1次/周，共15周，于术后20、26、40周分批取出食管标本，用SABC法免疫组化染色检测食管上皮中增殖细胞核抗原（PCNA）的表达，制备食管粘膜组织单细胞悬液，经DNA染色后行流式细胞仪检测，分析样品的DNA指数（DI），增值指数（PI）及DNA非整倍体率，结果显示，各组的PCNA标记指数（LI）均随时间延长而显著增加，各时间点反流组的LI增加均较对照组更为明显，D、DG组又较G组高，随反流和诱癌时间的延长各组食管上皮的平均DI及PI亦逐渐增加，非整倍体率逐渐增高，反流各组的增加程度比C组显著更高，其中D组、DG组最为显著，提示各种类型食管反流均可致食管上皮细胞增殖异常及DNA含量异常，并促进细胞恶性增殖的发生，有十二指肠内容物反流的组内细胞增殖异常更为明显，细胞增殖异常与食管肿瘤的发生率有密切关系。

EPITHELIAL CELL PROLIFERATION AND DNA PLOIDY PATTERN IN ESOPHAGEAL TUMOR INDUCED BY GASTRIC REFLUX

The aim is to study proliferation of esophageal epitheliun with reflux of different gastrointestin secretions to the esophagus and its role in carcinogenesis of esophagus. Gastroesophageal reflux(G), duodenoesophageal reflux(D) and duodenogastroesophageal reflux(DG) model and control group(C) were reproduced by operations. All rats were given carcinogen (methyl n amyl nitrosamine). Then their esophagi were harvested at 20, 26,and 40 weeks after the operation. With immunohistochemical staining of SABC method, PCNA labeling indexes(LI) were compared. Epithelial cells were stained with PI and assessed with flow cytometry(FCM).The results of FCM were compared in terms of DNA index(DI), proliferating index(PI) and aneuploidy. LIs increased with time of reflux and the administration of MANA. LIs in reflux groups, especially in D and DG group, were significantly greater than that in the C group with the same time interval. 3 indexes of FCM showed obvious changes in G, D and DG group, and they were greater than C group.The changes ware most marked in D and DG groups.It is concluded that all kinds of reflux into the esophagus can induce abnormal proliferation of esophageal epithelium and enhance carcinogenesis of the esophagus. The role of duodenoesophageal reflux may be more important than gastroesophageal reflux.