乳酸菌调控内质网应激在肠粘膜屏障损伤修复中的机制研究

项目名称： 乳酸菌调控内质网应激在肠粘膜屏障损伤修复中的机制研究

项目编号： No.81200264

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学一处

项目作者： 陈红旗

作者单位： 上海交通大学

项目金额： 23万元

中文摘要： 肠黏膜屏障损伤与诸多疾病发生发展密切相关，而肠上皮细胞（IEC）损伤的益生菌修复在维护肠屏障功能方面发挥着至关重要作用，但有关IEC损伤益生菌修复机制尚不清楚。我们前期实验发现IEC损伤益生菌修复伴有Grp78和IRE1表达活性降低以及NF-κB介导的促炎因子表达下调，提示内质网应激（ERS）介导的胞内信号通路参与了IEC损伤益生菌修复机制。为此，本课题通过人肠上皮细胞系Caco-2、IL-10-/- IEC及IL-10-/-小鼠模型和临床IBD肠标本，从分子、细胞、组织以及动物整体水平分别评价ERS和NF-κB信号通路间的调控关系，通过干预TLR、p38 MAPK、IRE1、Grp78、NF-κB等多个中间环节，阐明TLR- p38 MAPK- ERS（IRE1/XBP1）-NF-κB调控网络在IEC损伤益生菌修复中分子机制，对推进肠粘膜屏障损伤相关疾病的防治具有重要理论和实际参考价值。

中文关键词： 炎症性肠病；内质网应激；肠道菌群；宏基因组；植物乳杆菌

英文摘要： The intestinal mucosal barrier injury is closely related to the occurrence and development of many diseases, and the probiotic repair of intestinal epithelial cells (IEC) damage plays a crucial role in the maintenance of intestinal barrier function. However, the probiotic repair mechanism of IEC damage is unclear. Our previous experimental study found that the probiotic repair mechanism of IEC damage was coupled with the alteration of Grp78 and IRE1 expression and NF-κB-mediated proinflammatory cytokines expression, suggesting that endoplasmic reticulum stress (ERS)-mediated intracellular signaling pathway involved in the probiotic repair mechanism of IEC damage. To this end, from the molecular, cellular, organizations, and animals levels, the regulation of relations between the ERS and NF-κB signaling pathway were evaluated In the subject of human intestinal epithelial cell line Caco-2, IL-10-/ - IEC and IL-10-/ - mouse model and clinical IBD intestinal specimens,through the intervention of many intermediate factors as TLR ,p38 MAPK, IRE1,Grp78, NF-kappa B and so on, eventually to clarify the role of TLR-p38 MAPK-ERS (IRE1/XBP1)-NF-κB regulatory network in the specific probiotic repair mechanism of IEC damage.In this respect, it has important theoretical and practical value for promoting the understanding of t

英文关键词： inflammatory bowel disease；endoplasmic reticulum stress；intestial flora；metagenome；Lactobacillus plantarum