5-HT调控仔猪肠上皮细胞更新及紧密连接蛋白Occludin表达的"5-HTR—VIP"能神经通路

随着集约化养殖和环境应激因素增加，应激性胃肠紊乱的神经调控成为生命领域研究的"热点"。机体95%的5-HT存在于胃肠道，应激引起5-HT增加，信号传导异常，导致腹泻。前期研究发现肠黏膜中富含5-HT、VIP能神经纤维，二者呈正相关。肠上皮细胞作为肠黏膜屏障的重要组成单位，5-HT调控肠上皮细胞结构、功能的研究很少。因此，本项目提出5-HT调控肠黏膜上皮细胞更新和细胞连接构建的受体-神经作用通路的设想。本课题利用添加递质、受体阻断、体内与体外实验、仔猪感染腹泻等实验手段，检测肠黏膜上皮超微结构与细胞生物活性、T-J蛋白occludin的表达、5-HT受体以及肠隐窝上皮细胞增殖分化，阐明5-HT调控肠黏膜上皮细胞更新和紧密连接蛋白表达的"5-HTR-VIP"能神经通路。以期全面解析神经调控肠黏膜屏障建设的动态变化规律和分子基础，揭示应激性腹泻的发生机制，为应激性胃肠功能紊乱的诊治提供新的突破点

With the intensive livestock development and stresses factors increasing, the study on nerve regulation of intestinal function abnormal becomes to the "hot spot" in the field of life science. 95% 5-HT locates in the gastrointestinal tract under physiological status, but it increases and signal transmits abnormally under stress, which will cause diarrhea. Previous study find that 5-HT、VIP nerve are rich in intestinal mucous membrane, and both are positive correlation. Intestinal epithelium is an important unit of intestinal mucous barrier. However, the regulation of 5-HT on intestinal epithelium structure and function is still unclear. Therefore, we propose the assume that the "receptor- nerve" pathway of 5-HT on the IEC renovation and cell junction. The project explore to ultrastructure and cell activation of IEC, the expression of tight junction protein (occludin),5-HT receptors and the proliferation and differentiation of IEC in intestinal crypt by use of the neurotransmitter adding, nerve receptors blocking, the incorporation of in vivo and in vitro and the diarrhea model of piglet. It is expected that the regular pattern development and molecule foundation of the intestinal mucosal barrier reconstruction is resolved roundly, and next the mechanism of stress diarrhea is clearer in the future.