针对脑死亡和冷藏后的肾脏炎症：研究 NLRP3 炎症体抑制剂 (MCC950) 用于预处理供体肾脏的潜力。
Targeting Kidney Inflammation After Brain Death and Cold Storage: Investigating the Potential of an NLRP3 Inflammasome Inhibitor (MCC950) for Preconditioning Donor Kidneys.
发表日期：2024 Sep 30
作者：
Naiane do Nascimento Gonçalves, Heloisa Cristina Caldas, Ludimila Leite Marzochi, Maria Alice Sperto Ferreira Baptista, Cristiano de Jesus Correia, Ana Cristina Breithaupt Faloppa, Luiz Felipe Pinho Moreira, Mario Abbud-Filho
来源：
TRANSPLANTATION
摘要：
脑死亡（BD）和冷藏（CS）是诱发供体肾脏炎症、损害器官质量的关键因素。我们研究了用炎性体 Nod 样受体家族 Pyrin 结构域 3 (NLRP3) 抑制剂 (MCC950) 治疗 BD 大鼠的肾脏，然后进行 CS 治疗是否可以减轻肾脏炎症。BD 大鼠被分配到 MCC950 治疗组或未治疗组 (NT)。在 CS 之前 (T0) 以及 CS 12 小时 (T12) 和 24 小时 (T24) 后立即评估肾脏。评估平均动脉压、血清肌酐、基因/蛋白质表达和组织学。在T0时，MCC950治疗不影响平均动脉压，但倾向于降低血清肌酐并改善急性肾小管坏死的组织学评分。然而，MCC950 降低了 NLRP3、caspase-1、白介素 (IL)-1β、IL-6、Kim-1、核因子 kappa B、肿瘤坏死因子 α 和 caspase-3 基因表达，同时增加了 IL-10 细胞因子基因表达。 CS 12小时后，仅NLRP3和caspase-1基因的表达下降，CS 24小时后，没有观察到基因表达谱的进一步变化。炎性体蛋白 NLRP3、caspase-1 和 IL-1β 的水平在所有时间点（T0、T12 和 T24）持续下降。这些发现表明，MCC950 治疗有望减轻 BD 和 BD 后肾脏中观察到的促炎状态。 CS.版权所有 © 2024 Wolters Kluwer Health, Inc. 保留所有权利。
Brain death (BD) and cold storage (CS) are critical factors that induce inflammation in donor kidneys, compromising organ quality. We investigated whether treating kidneys from BD rats with an inflammasome Nod-like receptor family pyrin domain containing 3 (NLRP3) inhibitor (MCC950) followed by CS could reduce kidney inflammation.BD rats were assigned to MCC950-treated or nontreated (NT) groups. Kidneys were evaluated immediately before CS (T0) and after 12 h (T12) and 24 h (T24) of CS. Mean arterial pressure, serum creatinine, gene/protein expression, and histology were evaluated.At T0, MCC950 treatment did not affect mean arterial pressure but tended to reduce serum creatinine and ameliorated the histological score of acute tubular necrosis. However, MCC950 reduced NLRP3, caspase-1, interleukin (IL)-1β, IL-6, Kim-1, nuclear factor kappa B, tumor necrosis factor alpha, and caspase-3 gene expression while increasing IL-10 cytokine gene expression. After 12 h of CS, only the expression of the NLRP3 and caspase-1 genes decreased, and after 24 h of CS, no further changes in the gene expression profile were observed. The levels of the inflammasome proteins NLRP3, caspase-1, and IL-1β consistently decreased across all time points (T0, T12, and T24).These findings suggest that MCC950 treatment holds promise for mitigating the proinflammatory state observed in kidneys after BD and CS.Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.