Wang Xinyue, Li Ning, Han Lu, Qiao Ou, Chen Xin, Wang Pengtao, Zhang Lancao, Hou Yingjie, Bao Fengjiao, Hao Herui, Saeed Sania, Zhang Li, Li Zizheng, Duan Xiaohong, Rao Shuquan, Liu Zichuan, Gong Yanhua
School of Disaster and Emergency Medicine, Faculty of Medicine, Tianjin University, No. 92 Weijin Road, Nankai District, Tianjin, 300072, China.
Institute of Disaster and Emergency Medicine, Faculty of Medicine, Tianjin University, Tianjin, China.
Nat Commun. 2025 Jan 26;16(1):1044. doi: 10.1038/s41467-025-56353-4.
Rhabdomyolysis or Crush syndrome-related AKI (RM/CS-AKI) has high mortality, and there is no effective early on-site treatment method. The critical pathogenic factor of RM/CS-AKI is the excessive free myoglobin (Mb) in blood circulation. Here, based on the concept of creating a "mobile barrier", we develop an anti-Mb rabbit monoclonal antibody (RabMAb) with high specificity, affinity, stability, and broad species reactivity. A single dose of anti-Mb RabMAb injection is sufficient for emergency rescue in both homologous and heterologous RM/CS-AKI male animal models. The main goal of blocking the passage of free Mb through the glomerular filtration barrier has been achieved by using the anti-Mb RabMAb, which has a long-term stable therapeutic effect within 14 days and promotes phagocytosis of Mb. The optimal administration strategy, pharmacokinetic analysis, toxicity evaluation for anti-Mb RabMAb, and the distribution of its immune complexes in RM/CS-AKI mice are investigated. Thus, we develop effective prevention and control strategies for RM/CS-AKI.
横纹肌溶解或挤压综合征相关急性肾损伤（RM/CS-AKI）死亡率高，且尚无有效的早期现场治疗方法。RM/CS-AKI的关键致病因素是血液循环中游离肌红蛋白（Mb）过多。在此，基于创建“移动屏障”的概念，我们开发了一种具有高特异性、亲和力、稳定性和广泛物种反应性的抗Mb兔单克隆抗体（RabMAb）。单剂量注射抗Mb RabMAb足以在同源和异源RM/CS-AKI雄性动物模型中进行紧急救援。通过使用抗Mb RabMAb实现了阻止游离Mb通过肾小球滤过屏障的主要目标，其在14天内具有长期稳定的治疗效果，并促进Mb的吞噬作用。研究了抗Mb RabMAb的最佳给药策略、药代动力学分析、毒性评估及其免疫复合物在RM/CS-AKI小鼠中的分布。因此，我们制定了RM/CS-AKI的有效防控策略。
