幽门螺杆菌通过细胞自噬影响胃黏膜上皮细胞DNA损伤修复的机制研究

细胞自噬对促进DNA损伤修复、维护细胞基因组稳定发挥重要作用，但其在Hp感染致病中的作用尚不明确。我们前期研究发现Hp感染可诱导胃黏膜上皮细胞发生DNA双链断裂（DSBs），并激活细胞DNA损伤反应信号通路；而当Hp持续感染时，我们观察到胃黏膜上皮细胞自噬水平抑制及同源重组（HR）修复关键蛋白Rad51表达下调的现象；促进自噬对Hp诱导胃黏膜细胞发生DSBs具有保护作用，但其机制尚不清楚。本研究将在前期基础上，通过体内外实验研究明确自噬相关蛋白与Rad51在胃黏膜癌变过程中变化及其与Hp感染的关系；阐明自噬对Hp感染胃黏膜上皮细胞生物学表型及DNA损伤修复的影响；揭示自噬对胃黏膜上皮细胞基因组稳定的保护机制。研究结果将有望进一步阐明Hp感染致病的分子机制，并为Hp感染相关疾病的防治提供新靶点。

Autophagy plays an important role in promoting DNA damage repair and maintaining the genomic stability, however, its role in the pathogenesis of H. pylori infection is unclear. Our previous study found that H. pylori infection could induce DNA double strand breaks(DSBs) in gastric epithelial cells, and actived DNA damage response pathway. We also observed the autophagy inhibited and Rad51 down regulated in gastric epithelial cells while persistent infected with H. pylori. Promoting autophagy has protective effect on DSBs induced by H. pylori，but the mechanism is unclear. We will continue further research in vitro and in vivo based on the previous study. Try to detect the expression of autophagy related protein and Rad51 on the different lesions of gastric mucosa and its relationship with H. pylori infection; Try to clarify the effect of autophagy on gastric biological phenotype and DNA damage repair in gastric mucosal infected with H. pylori; Try to reveal the genomic stability protective mechanism of autophagy in gastric epithelial cell. These results are expected to further elucidate the molecular mechanism of H. pylori infection and provide a new target for the prevention and treatment of H. pylori infection related diseases.