TIMP-2促进铁死亡参与肾脏缺血再灌注损伤的作用机制研究

急性肾脏损伤（Acute kidney injury，AKI）是ICU常见并发症，合并AKI患者死亡风险增加，肾缺血再灌注损伤（Ischemia-reperfusion injury，IRI）是AKI的重要病因之一。IRI的发生机制复杂，铁死亡是其发生的重要机制之一。我们发现TIMP-2可作为预测心脏术后AKI的早期标志物，具有较高诊断价值。然而TIMP-2是否参与IRI肾脏损伤过程尚不清楚。我们预实验证实TIMP-2可调控Eratin诱导的肾小管上皮细胞的铁死亡，并影响铁自噬水平。因此我们推测TIMP-2可调控铁自噬导致铁死亡，引起肾脏缺血再灌注损伤。本研究通过体内体外实验，探索TIMP-2通过调控NCOA4介导的铁自噬促进铁死亡，并阐明该过程参与IRI的分子机制，为临床肾脏损伤干预提供新方向。

Acute kidney injury (AKI) is a common complication in ICU, and patients with AKI have an increased risk of death. Kidney ischemia-reperfusion injury (IRI) is one of the important causes of AKI. The mechanism of IRI is complex, and ferroptosis is one of the important mechanisms in IRI. We found that TIMP-2 could be used as an early biomarker to predict AKI after cardiac surgery and had a high diagnostic value. However, it is still unclear whether TIMP-2 is involved in the process of renal injury of IRI. Our preliminary experiments confirmed that TIMP-2 could regulate Eratin-induced ferroptosis and affect ferritinophagy in renal tubular epithelial cells. Therefore, we speculated that TIMP-2 could regulate ferritinophagy to cause ferroptosis in renal ischemia reperfusion injury. In this study, we conducted experiments in vivo and in vitro to explore the role of TIMP-2 in regulating NCOA4-mediated ferritinophagy to promote ferroptosis, and to clarify the molecular mechanism of this process involved in IRI, providing a new direction for clinical kidney injury intervention.