肠上皮细胞屏障在炎症性肠病（IBD）发生中有着重要地位。Slc26A3是Cl-/HCO3-离子交换体，我们前期研究证实Slc26A3的缺乏会削弱HCO3-/黏液屏障，但其对上皮细胞屏障的作用并不清楚。本课题组前期研究结果显示在小鼠结肠炎模型中Slc26A3表达下调，Slc26A3-/-小鼠细胞间紧密连接蛋白表达异常，提示其在上皮屏障中有着重要作用。我们进一步研究发现Slc26A3-/-小鼠结肠TNF-α水平增高，据此推测Slc26A3缺失可通过上调TNF-α影响上皮细胞屏障。因此，本研究拟构建Slc26A3siRNA和Slc26A3高表达慢病毒荧光表达载体，观察其对上皮屏障的影响，从细胞和动物水平研究沉默Slc26A3通过MAPK/NF-κB上调TNF-α表达的分子机制，阐明Slc26A3、MAPK/NF-κB、TNF-α与上皮屏障之间的关系及其分子机制，以期从中寻找IBD的潜在干预靶点。

Inflammatory bowel disease(IBD) is a chronic non-specific intestinal inflammation, and the incidence is worldwide increasing in recent years. Though the pathogenesis is not totally clear, the damage of epithelial barrier is known to be the central role in the process of onset of intestinal inflammation.Slc26A3 ion transporter is a Cl-/HCO3- exchanger, and in our previous studies, we demonstrated that Slc26A3 deficiency is associated with loss of colonic HCO3- secretion, absence of a firm mucus layer, and HCO3-/mucus barrier impairment in mice. However, whether Slc26A3 had an effect on intestinal epithelial barrier is not clarified yet. Our researches demonstrated that Slc26A3 mRNA and protein expression dramatically decreased in DSS-induced colitis in mice and the tight junction and adherent junction protein expressions were also modified in Slc26A3-/- mice, thus it suggested that Slc26A3 play an important role in epithelial barrier. According to our further studies, we found that the absence of Slc26A3 can upregulate the level of TNF-α, therefore, we pose a hypothesis that the absence of Slc26A3 can exacerbate colon inflammation by increasing TNF-α expression. Based on the present theories and our experiments, we intend to over-express or silence the Slc26A3 gene expression in colon epithelial cells, to observe the corresponding changes of the integrity of epithelial barrier ,then detect the molecular mechanisms of silencing Slc26A3 upregulate TNF-α through MAPK/NF-κB pathway in cell and animal level. In this way we want to illustrate the role and mechanisms of Slc26A3 enhancing the epithelial barrier function to explore potential intervention targets of IBD.