已有的动物研究表明雌激素可抑制草酸钙结石的形成，但临床试验却发现补充雌激素并不能有效降低绝经女性肾结石的发病率，提示雌激素受体（ER）可能在结石形成过程中具有重要调控作用。我们前期研究发现ERβ在女性草酸钙结石患者肾组织的表达显著降低，且ERβ拮抗剂可明显促进小鼠肾脏草酸钙结晶的形成，初步证实ERβ参与了草酸钙结石形成的调控。我们进一步研究发现ERβ可以调控NADPH氧化酶相关基因的表达、活性氧释放以及肾小管上皮细胞的氧化应激损伤，而肾小管上皮细胞的氧化应激损伤恰恰是草酸钙结石形成的关键步骤之一，但ERβ调控NADPH氧化酶以及草酸钙结石形成的具体机制仍不清楚。因此，本项目拟通过细胞模型和ERβ全身敲除、肾脏靶向敲除小鼠模型进一步证实并揭示ERβ调控NADPH氧化酶和草酸钙结石形成的作用及分子机制，从而为深入揭示草酸钙结石的发病机制和临床防治提供新的实验依据和干预策略。

Previous animal studies have shown that estrogen could inhibit calcium oxalate (CaOx) stone formation. However, clinical studies data indicated that the estrogen supplement therapy failed to reduce the risk of stone formation in menopause female effectively, suggesting that estrogen receptor (ER) may play an important role in CaOx stone formation. Our preliminary data revealed that the expression of ERβ in renal epithelial tissue was significantly down-regulated in female patients with CaOx stones, and increased crystals were observed in female mice treated with ERβ antagonist compared to that in control group, indicating that ERβ is involved in the regulation of CaOx crystals formation. In addition, we found that silencing the endogenous expression of ERβ could augment oxalate-induced oxidative injury in renal epithelial cells , which is one of the critical mechanisms for CaOx stone formation, via increasing the expressions of NADPH oxidase related genes and releases of reactive oxygen species, but the underlying mechanism remains unclarified. In the present project, we will further investigate and reveal the role and mechanism of ERβ in the regulation of NADPH oxidase and CaOx stone formation via using cells and ERβ knockout mice models, thus providing new experimental evidences for the pathogenesis of CaOx stone formation and new clinical intervention strategies for the prevention and therapy of CaOx stones.