瞬时受体电位通道7（TRPM7）属于TRPM亚家族中的一员，其激活可介导Ca2+等内流，参与氧化应激、炎症等病理反应过程。铁死亡是2012年发现的一种新型细胞死亡方式，与神经元损伤等病理过程有关。我们前期研究证实在类风湿关节炎（RA）患者和佐剂型关节炎（AA）大鼠关节软骨细胞中存在铁死亡，且阻断TRPM7对其有保护作用。在此基础上试图（1）使用TRPM7特异性阻断剂、激动剂、过表达或shRNA质粒，分析其对Erastin诱导的AA大鼠关节软骨细胞铁死亡的调控作用。（2）运用全细胞膜片钳、激光共聚焦显微镜等，分析Ca2+及其下游PKC/NOX4/ROS信号在TRPM7调控软骨细胞铁死亡中的作用。（3）体内给予TRPM7与铁死亡特异性抑制剂，分析TRPM7、铁死亡与RA软骨细胞损伤之间的内在联系。初步阐明TRPM7在AA大鼠关节软骨细胞铁死亡中的作用及可能机制，为RA的治疗提供新的靶点。

Transient receptor potential melastatin 7, TRPM7, is a member of the TRPM subfamily and has a dual function of cation channel and kinase activity. TRPM7 activation can lead to extracellular Ca2+ and other ion influx, and thus and participates in pathological processes such as oxidative stress and inflammation. Ferroptosis is a new type of cell death that was discovered in 2012 and is different from apoptosis and necrosis. Ferroptosis is related to pathological processes such as tumor suppression and neuronal damage. Our previous study have been confirmed that ferroptosis existed in articular chondrocytes of rheumatoid arthritis (RA) patients and adjuvant arthritis (AA) rats, and blocking TRPM7 has a protective effect on chondrocyte ferroptosis. On this basis, we attempted to use TRPM7 specific blockers, agonists, overexpression or shRNA plasmids to analyze the effect of TRPM7 on Erastin-induced ferroptosis in articular chondrocytes of AA rats in vitro. Moreover, TRPM7 currents are recorded with whole-cell patch-clamp and fast-perfusion techniques, and intracellular calcium ([Ca2+]i) in chondrocytes are recorded by using the laser scanning confocal microscopy. We analyzed the role of TRPM7-mediated Ca2+ overload and its downstream PKC/NOX4/ROS signaling pathway in chondrocyte ferroptosis. Furthermore, the TRPM7-specific blocker and the ferroptosis-specific inhibitor Ferrostatin-1 were administered in vivo to analyze the relationship between TRPM7, ferroptosis and RA chondrocyte injury. In this research proposal, we try to preliminarily clarify the protective effect and mechanism of blocking TRPM7 on ferroptosis of articular chondrocytes of rats with adjuvant arthritis. Therefore, we hypothesized that inhibiting TRPM7 would provide protection for the articular cartilage in adjuvant arthritis (AA) rats via reducing chondrocyte ferroptosis, and can be used as potent therapeutic targets for the treatment of cartilage destruction diseases including RA in future.