嗜酸乳杆菌对断奶仔猪肠黏膜屏障损伤的保护作用及其通过NF-κB信号通路调控屏障功能的作用机制

断奶应激常常导致仔猪肠黏膜损伤，肠道屏障功能下降。研究表明，嗜酸乳杆菌对肠黏膜屏障功能具有良好的保护和修复作用。嗜酸乳杆菌上调肠道上皮细胞紧密连接蛋白Occludin、Claudin-1、ZO-1的表达及调节NF-κB信号通路可能为其促进肠道屏障功能发挥了积极作用。但有关其作用机理尚不明确。本项目拟在前期工作的基础上，运用营养学、细胞系模型、免疫印迹、PCR、共聚焦显微定位等技术手段：（1）明确嗜酸乳杆菌与仔猪上皮细胞紧密连接蛋白及屏障功能之间的内在关系；（2）阐明嗜酸乳杆菌发挥调节屏障功能的主要效应分子及其抑制NF-κB的关键蛋白因子；（3）揭示嗜酸乳杆菌通过NF-κB信号通路保护仔猪肠黏膜屏障功能的作用机制。研究结果将为系统解释嗜酸乳杆菌调控仔猪肠黏膜屏障功能的作用机制提供必要的理论依据，并为生产中减缓因断奶应激导致的仔猪肠黏膜损伤提供潜在的技术支持。

Weaning stress often leads to intestinal mucosal injury and decreased barrier function. Lactobacillus acidophilus has good protecting and repairing effects on the barrier function of intestinal mucosa. It is speculated according to studies that, up-regulating the expression of intestinal epithelial tight junction protein Occludin, Claudin-1 or ZO-1, and regulating NF-κB signal pathway may play apositive role. But its mechanism is still unknown. On the basis of previous studies, using the technological means of nutriology, cell line model, western blotting, PCR, confocal laser scanning and positioning microscopy and so on, this study is designed to: (1) define the internal relation between Lactobacillus acidophilus, tight junction protein and intestinal epithelial barrier function in; (2) illustrate the main effect or molecules of lactobacillus acidophilus which regulate the barrier function, and the key protein factor which inhibit NF-κB; (3) reveal the mechanism which lactobacillus acidophilus protect the barrier function of intestinal mucosa through NF-κB signal pathways. The study results will provide a necessary theoretical basis for systematically interpreting the mechanism of Lactobacillus acidophilus regulating the barrier function of intestinal mucosa and a potential technical support to relieve the intestinal mucosal injury cause by weaning stress.