阻断成纤维细胞来源的HB-EGF和BMP4逆转Barrett食管的实验研究

项目名称： 阻断成纤维细胞来源的HB-EGF和BMP4逆转Barrett食管的实验研究

项目编号： No.81200261

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学一处

项目作者： 陈鑫

作者单位： 天津医科大学

项目金额： 24万元

中文摘要： Barrett食管（BE）是食管腺癌发生的重要过程，一旦形成很难逆转。既往认为是酸或/和胆盐直接刺激食管鳞皮上调Cdx2的结果。但我们应用酸或胆盐刺激食管复层鳞状上皮体外模型仅导致其细胞间通透性增加而不能上调Cdx2。最近研究发现食管间质细胞在BE发生中有重要作用，其产生的HB-EGF和BMP4可以上调食管鳞皮Cdx2表达。因此推测酸或胆盐破坏食管上皮细胞间紧密连接，刺激位于其下方的间质细胞产生HB-EGF和BMP4，进而反作用于食管鳞皮导致BE。本研究拟观察BE患者治疗后食管间质EGF和BMP4的水平；采用酸和胆盐刺激的食管复层鳞皮与成纤维细胞共培养的模型，用免疫组化和分子生物学的方法，观察成纤维细胞产生的HB-EGF和BMP4直接对食管鳞皮Cdx2表达及阻断上述因子后的变化；比较BE动物模型中，抑制酸碱和阻断EGF、BMP4后食管上皮Cdx2表达及细胞形态变化，为逆转BE提供新靶点。

中文关键词： 成纤维细胞；气-液交界培养；Barrett食管；BMP4；

英文摘要： Barrett's esophagus (BE) is crucial for the progression of esophageal adenocarcinoma, it is difficult to reverse once it happened. Previously, it considered to be the result of up-regulation of Cdx2 which were caused by directing stimulate the esophagus epithelial by acid or/and bile saltsion. However, in our study, with the application of acid or bile salts stimulating the esophageal stratified squamous epithelium in vitro, we found it can increase cell permeability, but the upregulation of Cdx2 is not discovered. Recent studies have suggested that the esophageal stromal is crucial for the progression of BE, HB-EGF and BMP4 which were derived from fibroblast can up-regulate the expression of esophagus Cdx2.It thought to be that the acid or bile salts could damage the esophageal epithelial cell tight junctions and stimulate the mesenchymal cells adjacent, then the mesenchymal cells can release HB-EGF and BMP4 which in turn reacts on the esophagus squamous epithelium and cause BE. The present project will detect the changing of the EGF and BMP4 in BE patient after therapy. With the co-cultured model of esophageal acid and bile salts stimulate stratified cell and fibroblast cells, immunohistochemistry and molecular biology methods were used to confirm the expression of Cdx2 when HB-EGFand BMP4 were induced or bloc

英文关键词： fibroblast；air-liquid interface culture；Barrett esophagus；BMP4；