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一种用于监测铁死亡过程中脂滴变化的亚铁荧光寿命响应探针及其在肝病模型中的成像。

A ferrous fluorescence lifetime response probe for monitoring changes in lipid droplets during ferroptosis and imaging in liver disease model.

机构信息

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, No.163 Xianlin Road, Nanjing, 210023, China.

Pancreas Center, The First Affiliated Hospital of Nanjing Medical University, Jiangsu Province Hospital, Nanjing, 210029, China.

出版信息

Biosens Bioelectron. 2025 Jan 1;267:116742. doi: 10.1016/j.bios.2024.116742. Epub 2024 Sep 4.

DOI:10.1016/j.bios.2024.116742
PMID:39243450
Abstract

Ferrous ions (Fe⁺) accumulation and abnormal alterations in lipid droplets (LDs) are closely associated with ferroptosis. In the liver, excessive iron accumulation promotes oxidative stress and exacerbates lipid droplet accumulation, while the disruption of iron homeostasis may also affect the formation and size of lipid droplets, their increased number and size can exacerbate the severity of disease under fatty liver conditions. The leads to hepatocyte damage, further triggering liver inflammation, fibrosis, and ultimately resulting in cirrhosis and hepatocellular carcinoma. Therefore, real-time monitoring of iron ion and lipid droplet changes is crucial for assessing the severity of liver disease, disease progression, and understanding the mechanisms of ferroptosis. We have developed a fluorescent probe, NRFep, for real-time monitoring of iron ion fluctuations and visualization of lipid droplet changes in ferroptosis and liver disease models. NRFep is specific and sensitive to iron ions and exhibits excellent stability in both cells and animal models. In addition, NRFep can be used to monitor changes in iron ions and lipid droplets in mouse liver injury and fatty liver models. Through fluorescence lifetime imaging technology, NRFep can also study the dynamic changes of intracellular iron ion content. NRFep provides a powerful tool for studying ferroptosis and related diseases, and its unique dual-monitoring function opens up new possibilities for developing new diagnostic and therapeutic strategies.

摘要

亚铁离子(Fe⁺)的积累和脂滴(LDs)的异常改变与铁死亡密切相关。在肝脏中,过量的铁积累会促进氧化应激,加剧脂滴的积累,而铁平衡的破坏也可能影响脂滴的形成和大小,其数量和大小的增加会加剧脂肪肝情况下疾病的严重程度。这会导致肝细胞损伤,进一步引发肝脏炎症、纤维化,最终导致肝硬化和肝癌。因此,实时监测铁离子和脂滴的变化对于评估肝脏疾病的严重程度、疾病进展以及理解铁死亡的机制至关重要。我们开发了一种荧光探针 NRFep,用于实时监测铁离子波动和可视化铁死亡和肝脏疾病模型中的脂滴变化。NRFep 对铁离子具有特异性和敏感性,在细胞和动物模型中均表现出优异的稳定性。此外,NRFep 可用于监测小鼠肝损伤和脂肪肝模型中铁离子和脂滴的变化。通过荧光寿命成像技术,NRFep 还可以研究细胞内铁离子含量的动态变化。NRFep 为研究铁死亡和相关疾病提供了有力的工具,其独特的双重监测功能为开发新的诊断和治疗策略开辟了新的可能性。

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