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半胱氨酸引发的级联反应形成香豆素:通过近红外荧光探针可视化酒精性肝病中的半胱氨酸波动。

Cysteine triggered cascade reaction forming coumarin: Visualization of cysteine fluctuation in alcoholic liver disease by a NIR fluorescent probe.

机构信息

Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Chemical Biology Key Laboratory of Hebei Province, State Key Laboratory of New Pharmaceutical Preparations and Excipients, College of Chemistry and Materials Science, Hebei University, Baoding 071002, PR China.

Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of the Ministry of Education, Chemical Biology Key Laboratory of Hebei Province, State Key Laboratory of New Pharmaceutical Preparations and Excipients, College of Chemistry and Materials Science, Hebei University, Baoding 071002, PR China.

出版信息

Spectrochim Acta A Mol Biomol Spectrosc. 2025 Jan 5;324:124974. doi: 10.1016/j.saa.2024.124974. Epub 2024 Aug 13.

Abstract

Alcoholic liver disease (ALD) is a chronic toxic liver injury caused by long-term heavy drinking. Due to the increasing incidence, ALD is becoming one of important medical tasks. Many studies have shown that the main mechanism of liver damage caused by large amounts of alcohol may be related to antioxidant stress. As an important antioxidant, cysteine (Cys) is involved in maintaining the normal redox balance and detoxifying metabolic function of the liver, which may be closely related to the pathogenesis of ALD. Therefore, it is necessary to develop a simple non-invasive method for rapid monitoring of Cys in liver. Thus, a near-infrared (NIR) fluorescent probe DCI-Ac-Cys which undergoes Cys triggered cascade reaction to form coumarin fluorophore is developed. Using the DCI-Ac-Cys, decreased Cys was observed in the liver of ALD mice. Importantly, different levels of Cys were monitored in the livers of ALD mice taking silybin and curcumin with the antioxidant effects, indicating the excellent therapeutic effect on ALD. This study provides the important references for the accurate diagnosis of ALD and the pharmacodynamic evaluation of silybin and curcumin in the treatment of ALD, and support new ideas for the pathogenesis of ALD.

摘要

酒精性肝病 (ALD) 是由长期大量饮酒引起的慢性中毒性肝损伤。由于发病率的增加,ALD 成为重要的医学任务之一。许多研究表明,大量饮酒引起肝损伤的主要机制可能与抗氧化应激有关。半胱氨酸 (Cys) 作为一种重要的抗氧化剂,参与维持肝脏正常的氧化还原平衡和解毒代谢功能,这可能与 ALD 的发病机制密切相关。因此,有必要开发一种简单的非侵入性方法来快速监测肝脏中的 Cys。因此,开发了一种近红外 (NIR) 荧光探针 DCI-Ac-Cys,它通过 Cys 触发级联反应形成香豆素荧光团。使用 DCI-Ac-Cys,观察到 ALD 小鼠肝脏中的 Cys 减少。重要的是,用抗氧化剂水飞蓟宾和姜黄素治疗的 ALD 小鼠肝脏中监测到不同水平的 Cys,表明对 ALD 具有极好的治疗效果。本研究为 ALD 的准确诊断和水飞蓟宾、姜黄素治疗 ALD 的药效学评价提供了重要参考依据,并为 ALD 的发病机制提供了新的思路。

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