植物乳杆菌激活NHE8信号通路并在炎症性肠病中发挥保护作用可能的机制探究

我国益生菌基础研究相对滞后于益生菌产业的发展。本课题组与美国亚利桑那大学医学院胃肠病学研究室在前期研究中发现，最新确认的钠氢转运体家族成员NHE8参与维持肠粘膜的完整性，而植物乳杆菌JDM1能够显著激活NHE8的表达。本课题组提出假说：植物乳杆菌可能通过上调NHE8的表达来调节肠道粘蛋白合成并参与维持肠道粘液层的正常结构，从而保持肠粘膜的完整性，可能是其对炎症性肠病治疗作用的机制之一。本课题组在对该菌株已进行全基因组测序的基础上，拟从体内和体外系列实验证实该假说。在不同小鼠模型中探究植物乳杆菌JDM1对NHE8及杯状细胞分泌粘蛋白的调节作用。并在细胞水平观察植物乳杆菌JDM1对NHE8及MUC2表达的调节作用并探究可能的信号转导机制。这些结果将有利于从新的视角认识植物乳杆菌JDM1保护肠粘膜完整性可能的机制，同时也能够进一步深入认识NHE8在肠道中的功能。

Development of basic research in probiotics is relatively lagging behind the probiotic industry in China. The research group completed the first whole genome sequencing work of Lactobacillus plantarum JDM1. In previous studies, the newly discovered sodium hydrogen transporter family member NHE8 was found involve in the maintenance of the intestinal mucosa, and L. plantarum JDM1 can activate the expression of NHE8. So we put forward the hypothesis: L. plantarum JDM1 could upregulate the expression NHE8 to regulate the intestinal mucin synthesis and participate in maintaining the normal structure of intestinal mucus layer,thus maintaining the integrity of the intestinal mucosa, may be is one of the mechanism in the treatment of inflammatory bowel disease . To verify this hypothesis, we will explore how L. plantarum JDM1 regulate the secretion of mucin in colon and whether NHE8 is the keypoint in this pathway in different animal models. And at the cellular level, we will explore possible signal transduction mechanism of L. plantarum JDM1 on the regulation effects of NHE8 and MUC2 expression . These results will be helpful to the understanding of mechanisms of L. plantarum JDM1 protecting the intestinal mucosal integrity, also could further understanding of NHE8 in the gut function, providing new scientific basis for this probiotic strain isolated from China in the treatment of inflammatory bowel disease.