结石可以促发肾脏炎症，且炎症程度与结石发展、复发明显相关。我们前期发现Sulforaphane通过NRF2-miR-93-TLR4/IRF1通路调控巨噬细胞极化缓解肾脏炎症损伤和结晶沉积。本项申请中，我们将在细胞、小鼠模型和临床样本中探究Sulforaphane对NRF2-miR-93-TLR4/IRF1通路的调控、miR-93-HDAC4-NRF2正反馈调控机制及其在巨噬细胞极化、炎性因子释放和细胞炎症损伤中的影响；阐明Sulforaphane在巨噬细胞对结晶的吞噬，草酸钙结晶的沉积及草酸钙肾结石的发生发展及复发中的作用及应用效果。我们还将首次利用PET-CT延迟显像技术与micro-CT及三维重建晶体沉积评估系统联合，动态及定量评价活体组织中炎症程度并在整体水平阐释结晶与炎症的联系。本项目的成功实施将丰富肾结石的发病分子机制，为肾结石精准化治疗提供新的策略和靶点。

Kidney stones can promote renal inflammation and the degree of inflammation is significantly associated with stone development and recurrence. Our previous study showed that Sulforaphane regulates macrophage polarization to alleviate inflammation damage and crystallization deposition in kidneys through NRF2-miR-93-TLR4/IRF1 pathway. In this application, we will explore the effects of Sulforaphane on the regulation of NRF2-miR-93-TLR4/IRF1 pathway, the positive feedback regulation mechanism of miR-93-HDAC4-NRF2 and their effects on macrophage polarization, inflammatory factor release and inflammatory damage in renal tubular epithelial cells, mouse model and clinical samples. Further more, we will elucidate the roles of Sulforaphane in macrophage phagocytosis, calcium oxalate crystallization deposition and the occurrence, development as well as the recurrence of calcium oxalate kidney stones.For the first time, this project will perform delayed imaging technology in PET-CT combined with micro-CT to evaluate the degree of inflammation in a dynamic and quantitative model and explain the relationship between crystallization and inflammation at the overall level. The successful implementation of this project will enrich the molecular mechanisms of renal calculi and provide new strategies and targets for the precise treatment of renal calculi.