氯离子/碳酸氢盐转运体Slc26a9对于十二指肠粘膜上皮细胞碳酸氢盐分泌调节的机制研究

消化性溃疡是消化系统的常见病、多发病。十二指肠粘膜的碳酸氢盐分泌是防止十二指肠粘膜损害的重要保护因素，受到相关离子通道蛋白的调节。Slc26a9是新近发现的一个碳酸氢盐转运通道，在十二指肠中存在表达但具体功能不清。我们的前期研究发现：Slc26a9的缺失会导致近端十二指肠碳酸氢盐分泌无论是在基础状态下还是在低酸刺激及cAMP激动剂forskolin的刺激下显著降低，并伴有水分泌及十二指肠粘液厚度的降低。提示：Slc26a9对于调节近端十二指肠碳酸氢盐的分泌及在十二指肠碳酸氢盐-粘液屏障保护机制中起着至关重要的作用。此外，相对于健康对照者，十二指肠溃疡的病人，无论是否感染了幽门螺旋杆菌，Slc26a9的mRNA表达均是明显降低的。进一步提示Slc26a9的下调涉及了十二指溃疡的发生。因此，本课题主要研究Slc26a9对于十二指肠粘膜上皮细胞碳酸氢盐分泌的调节以及在消化性溃疡发生发展中的作用。

peptic ulcer is a common diseases of digestive system. Duodenal mucusal bicarbonate (HCO3-) secretion plays an important role in duodenal mucosal protection against acid-peptic injury, which is regulated by some ion channels. Slc26a9 is a recently discovered bicarbonate transporter, which was detected in the duodenum, but the physiological function is unclear. Our previous preliminary experiments demonstrated that loss of Slc26a9 results in impairing proximal duodenal bicarbonate secretion both in basal state and after low acid as well as forskolin stimulation, acompanying with reduction of fluid secretion and mucus thickness, indicating that Slc26a9 plays a key role in regulating duodenal bicarbonate secretion and the protective mechanism of duodenal bicarbonate-mucus barrier function. In addition, expression of Slc26a9 in duodenal peptic patient was significantly lower when compared with health control and independent of Helicobacter pylori infection, suggesting that down-regulation of Slc26a9 was involved in the development of duodenal peptic. Therefore, the aim of this study is to investigate the role of Slc26a9 in regulating of duodenal bicarbonate secretion and its function in the development of duodenal peptic.