MR功能成像定量评价铁死亡介导肾缺血再灌注损伤的机制

Ischemia-reperfusion injury (IRI) is the primary cause leading to acute kidney injury and renal failure. Recent studies have confirmed that ferroptosis, as a form of iron-dependent cell death, played a pivotal role in the process of IRI. Quantitative susceptibility mapping (QSM) can accurately detect intracellular iron content by calculating the susceptibility of each voxel in the image. Based on the ability of QSM imaging to detect iron sensitively, we propose a hypothesis that multi-parameter MRI including QSM imaging can reflect ferroptosis-mediated IRI in the kidney energetically. Firstly, by observing the influence of different ischemic time on the MR parameters of renal cortex and medulla dynamically, the pathological scores, the quantized values of ferroptosis-related protein and gene, and renal iron content were used as the reference, to explicit that MR parameters can differentiate the degree of IRI in the kidney and its correlation with ferroptosis and IRI. Secondly, iron chelator was used to treat severe IRI. The dynamic changes of MR parameters of renal cortex and medulla, protein and genes related to ferroptosis, and renal iron content were observed at different time points after treatment, and to clarify the value of quantitative MR parameters in monitoring the treatment of IRI. The aim of the project is to reveal the mechanism of ferroptosis-mediated IRI by using multi-parameter MR imaging, which may open up a new way for quantitative diagnosis and monitoring the treatment of IRI.

缺血再灌注损伤（IRI）是引起急性肾损伤甚至肾衰竭的重要原因。最新研究证实铁死亡作为一种铁依赖的细胞死亡在肾IRI中起到关键作用。定量磁敏感图成像（QSM）是通过计算图像内每一体素的磁化率来反映细胞内铁含量。基于QSM技术敏感检测微量铁的能力，本项目提出包含QSM的多参数MRI成像能定量反映铁死亡介导肾IRI的假说。首先通过动态观察不同缺血时间对肾皮、髓质的MR参数值的影响，以肾IRI的病理评分、铁死亡相关蛋白和基因的表达量和肾铁含量做为参照，明确MR定量参数能鉴别肾IRI损伤程度的价值及其与铁死亡、肾IRI的相关性。其次利用铁螯合剂治疗重度肾IRI，观察治疗后不同时间点肾脏皮、髓质MR参数值、铁死亡相关蛋白和基因表达量、肾铁含量的变化，明确MRI定量参数在监测肾IRI治疗的价值。该研究旨在利用MRI多参数成像揭示铁死亡介导的肾IRI损伤机制，有望为肾IRI的定量诊断和治疗评价开辟新思路。

缺血再灌注损伤（IRI）是引起急性肾损伤甚至肾衰竭的重要原因。最新研究证实铁死亡作为一种铁依赖的细胞死亡在肾IRI中起到重要作用。定量磁敏感图成像（QSM）通过计算图像内每一体素的磁化率检测细胞内铁含量。基于QSM技术敏感检测微量铁的能力，本项目提出包含QSM的多参数MRI成像能定量反映铁死亡介导肾IRI的假说。首先通过动态观察不同缺血时间对肾皮、髓质的MR参数值的影响，以肾IRI的病理评分、铁死亡相关活性酶和基因的量化值和肾铁含量做为参照，明确MR定量参数能鉴别肾IRI损伤程度的价值及其与铁死亡、肾IRI的相关性。研究发现IRI组外髓质在IRI-pre、IRI-1h、IRI-12h、IRI-24h、IRI-48h时间点的磁化率值分别为(42.83±7.83)×10-3ppm、(-5.33±6.28)× 10-3ppm 、(6.50±3.94)× 10-3ppm、(12.00±3.74)× 10-3ppm、(22.00±6.81)× 10-3ppm，不同时间点的磁化率值差异有统计学意义(P < 0.001)。磁化率值与细胞水肿评分及GPX4平均光密度值呈负相关(ρ = -0.61, P = 0.002;ρ = -0.70, P < 0.001)。磁化率值与铁含量、坏死评分、间质炎症评分、铸型评分及肾损伤总病理评分呈正相关(ρ = 0.79, P < 0.001;ρ = 0.71, p < 0.001;ρ = 0.60, p = 0.002;ρ = 0.75, p < 0.001;ρ = 0.51, P = 0.01)。该研究利用QSM成像揭示铁死亡介导的肾IRI损伤机制，为肾IRI的定量诊断和治疗评价开辟新思路。