应激性胃粘膜损伤发病率高，危害严重，但损伤及炎症的机制不明。申请人团队前期发现特异性表达于胃粘膜的基因GKN2，最近发现应激时胃粘膜GKN2表达显著增加，GKN2可以通过外泌体在细胞间传递并上调NLRP3炎症小体在胃粘膜中的表达，促进胃粘膜的损伤；进一步发现，GKN2的表达受到糖皮质激素受体NR3C1调控。然而，GKN2在应激性胃粘膜损伤上的确切作用及机制尚不清楚。因此我们提出假说：应激后NR3C1感受激素水平的变化并激活GKN2，GKN2通过NLRP3炎症小体调节胃粘膜的炎症反应，进而加重胃粘膜细胞损伤。本课题将在前期基础上，通过细胞实验和小鼠胃粘膜损伤模型，从体内外水平研究NR3C1-GKN2-NLRP3炎症小体轴在应激性胃粘膜损伤神经-体液调节中的作用及机制。本项目的研究将为神经体液因素导致的应激胃粘膜损伤研究提供新的线索，为进一步防治胃粘膜损伤及发现新药靶点提供重要理论依据。

Stress-induced gastric mucosal lesion has a high incidence and serious damage, but the mechanism of injury and inflammation is unknown. Applicant team discovered the gastric mucosa-specific gene GKN2 in previous research. Our recent study found that GKN2 could be passed between cells by exosomes, up-regulate the expression of NLRP3 inflammasome in gastric mucosa and promote the damage of gastric mucosa. It is further found that the expression of GKN2 was regulated by the glucocorticoid receptor NR3C1. However, the exact role and mechanism of GKN2 in stress-induced gastric mucosal injury is unclear. Therefore, we propose hypotheses: NR3C1 senses changes in hormone levels and activates GKN2 after stress; GKN2 regulates gastric mucosal inflammatory response through NLRP3 inflammatory bodies, thereby aggravating gastric mucosal cell damage. In this study, we will explore the role and mechanism of NR3C1-GKN2-NLRP3 inflammatory body axis in the neurohumoral regulation of stress-induced gastric mucosa injury in vivo and in vivo by cell experiment and mouse gastric mucosal injury model. The study of this project will provide new clues for the study of stress gastric mucosal lesion caused by neuro-humoral factors, which will provide important theoretical basis for further prevention and treatment of gastric mucosal injury and discovery of new drug targets.