肾小管上皮细胞铁死亡促进肾脏缺血再灌注损伤的机制研究

肾小管上皮细胞铁死亡可诱发肾缺血再灌注损伤，目前，对铁死亡的研究是肾缺血再灌注损伤领域的前沿与热点。近年来研究表明，MicroRNA在细胞铁死亡中发挥重要作用，但铁死亡在肾缺血再灌注损伤过程中的具体细胞生物学机制尚不清楚。我们的前期结果显示肾小管上皮细胞铁死亡与miR-182-5p/miR-378a-3p信号通路关系密切，其可能负向调控GPX4/SLC7A11的蛋白表达。基于此，我们推测miR-182-5p/miR-378a-3p通过抑制GPX4/SLC7A11的翻译负向调控其蛋白的表达，促进肾小管上皮细胞铁死亡，加重肾缺血再灌注损伤。本项目拟以肾缺血再灌注损伤为研究对象，利用细胞分子生物学技术，通过体内外实验深入研究miR-182-5p/miR-378a-3p异常表达与肾小管上皮细胞铁死亡之间的关联，进一步阐明肾缺血再灌注损伤的发病机制，为有效缓解和治疗肾缺血再灌注损伤提供新的靶点。

Ferroptosis of renal tubular epithelial cells can induce renal ischemia-reperfusion injury. At present, the research on ferroptosis is the frontier and hot spot in the field of renal ischemia-reperfusion injury. Recent studies have shown that MicroRNA plays an important role in cellular ferroptosis. However, the specific cellular biological mechanism of ferroptosis in the process of renal ischemia-reperfusion injury is not clear. Our previous results show that ferroptosis in renal tubular epithelial cells is closely related to miR-182-5p/miR-378a-3p signaling pathway, which may negatively regulate the protein expression of GPX4 and SLC7A11. Based on this, we assume that miR-182-5p/miR-378a-3p negatively regulates its protein expression by inhibiting the translation of GPX4 and SLC7A11, which promotes ferroptosis in renal tubular epithelial cells and aggravates renal ischemia-reperfusion injury. The purpose of this project is to study the relationship between the abnormal expression of miR-182-5p/miR-378a-3p and ferroptosis in renal tubular epithelial cells by using cellular and molecular biology techniques in vivo and in vitro, so as to further clarify the pathogenesis of renal ischemia-reperfusion injury and provide a new target for effective relief and treatment of renal ischemia-reperfusion injury.