lncRNA NEAT1/miR122-5p/mRNA NFAT5通路调控尿毒症大鼠肠上皮细胞屏障损伤的分子机制研究

慢性肾脏病（CKD）持续进展将进入尿毒症阶段。微炎症状态（MIS），是普遍存在于CKD并随之加重的病理生理状态，与尿毒症的多种并发症息息相关。业已证实，肠道菌群结构改变和肠上皮屏障功能损伤是导致尿毒症患者MIS的重要原因。前期研究发现，尿毒症大鼠模型的肠粘膜通透性显著增高，免疫屏障功能显著下降。通过转录组基因分析发现，尿毒症大鼠肠粘膜中的lncRNA NEAT1与mRNA NFAT5表达量显著提高，且与此二者均相关的miR-122-5p表达显著降低。因此假设lncRNA NEATI/miR122-5p/mRNA NFAT5通路在尿毒症大鼠肠上皮细胞屏障损伤过程中发挥重要作用，对其调控可能修复尿毒症环境中受损的肠粘膜屏障。本项目拟通过细胞、动物和分子水平探究该通路在尿毒症肠黏膜屏障损伤发生机制中的作用。为改善肠粘膜屏障功能，减少尿毒症患者并发症、改善预后提供新思路。

Chronic kidney disease (CKD) will progress to uremia stage if it deteriorates continually. The micro-inflammatory state (MIS) is a pathophysiological state that is common in CKD and aggravated with the course of CKD. It has been confirmed that MIS is closely related to various complications of uremic patients. Furthermore, intestinal flora structure changes and intestinal epithelial barrier function damage are important causes of MIS in patients with CKD. In the previous experiments, we found that the intestinal mucosal permeability of the uremic rat model was significantly higher than that of normal rats, and the immune barrier function was significantly decreased. Through transcriptome gene analysis, we found that in the intestinal mucosa of uremic rats, the expression levels of two genes NEAT1 and NFAT5, which are closely related to cellular inflammatory response, were significantly increased, and the expression of their common miRNA---miR-122-5p was significantly reduced. Therefore, it was hypothesized that the lncRNA NEAT1/miR122-5p/mRNA NFAT5 pathway plays an important role in the intestinal epithelial cell barrier injury in uremic rats, and its regulation may help to repair the damaged intestinal mucosal barrier in uremia environment. This project aims to explore the role of lncRNA NEAT1/miR122-5p/mRNA NFAT5 pathway in the mechanism of uremia intestinal mucosal barrier damage at the cellular, animal and molecular levels. It provides new ideas for finding key targets for improving intestinal mucosal barrier function, reducing complications, and improving prognosis in uremic patients.