研究报道结肠腔内存在大量多巴胺（DA），其含量远高于结肠组织和血液。这些DA是否调节结肠黏膜屏障功能、是否在结肠上皮细胞内代谢尚不清楚。我们预实验发现：结肠上皮内含有大量代谢DA的酶；DA受体和转运体（DAT）广泛分布在结肠上皮细胞；离体结肠腔面膜侧给予DA显著升高黏膜中DA和DA代谢产物的含量，抑制DAT则明显减弱上述过程。我们还发现杯状细胞表达D5受体且调节结肠黏液分泌。我们推测结肠腔内DA可能作用于结肠黏膜上的DA受体调节黏膜屏障功能，并经DAT转入结肠上皮细胞内被其酶代谢分解。本研究拟采用DA受体基因敲除小鼠，结合在体灌肠/离体结肠黏膜/原代上皮细胞培养等，运用HPLC、同位素液闪计数和黏膜通透性检测等方法深入研究结肠腔内DA在结肠上皮细胞内的代谢及其对结肠黏膜屏障功能的影响，以期为结肠腔内DA的作用及其代谢过程提供理论和实验依据，为与黏膜屏障功能紊乱相关的疾病提供诊疗思路与靶点。

Accumulating evidence has shown that a substantial amount of free dopamine (DA) exists in colonic lumen. The level of DA in colonic lumen is much higher than that in colonic tissue or plasma. It is far from clear that whether the luminal DA could regulate the colonic mucosa barrier function or be metabolized in the colonic epithelium cells. Our preliminary data showed abundant expression of the metabolic enzymes of DA (MAO-A, MAO-B and COMT) in the colonic epithelial cells, and wide distribution of DA receptors and dopamine transporter (DAT) on the epithelial cell membrane. Administration of exogenous DA at the luminal side of the isolated colonic mucosa markedly elevated the levels of DA, DOPAC and HVA in the colonic tissue, which was inhibited by pretreatment with DAT inhibitor GBR12909. Besides, we also found the distribution of D5 receptors on the colonic goblet cells, while DA promoted colonic mucus secretion via D5 receptor. We presumed that the colonic luminal DA could regulate the colonic mucosa barrier function through combining with DA receptor. It also could be transported into colonic epithelium cells via DAT, where it would be metabolized by MAO and COMT. The present study aims to explore the process of the luminal DA metabolized in the colonic epithelium cells, and the role of the luminal DA on the regulation of colonic mucosa barrier function by DA receptor knockout mice, isolated colonic mucosa and primary cultured colonic epithelial cells, by means of HPLC/isotopic liquid scintillation counts/mucosal permeability measurement etc., which may provide a rationale for the function and metabolism of gut luminal DA and shed light on diagnosis and treatment of the colonic mucosa barrier disturbance associated diseases.