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基于纳米 MOFs 传感器对谷胱甘肽和磷酸盐的荧光成像评估甲状腺功能亢进诱导的肝损伤

Evaluating Hyperthyroidism-Induced Liver Injury Based on Fluorescence Imaging of Glutathione and Phosphate via Nano-MOFs Sensor.

机构信息

College of Chemistry, Chemical Engineering and Materials Science, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Institute of Biomedical Sciences, Shandong Normal University, Jinan 250014, P. R. China.

出版信息

Anal Chem. 2020 Jul 7;92(13):8952-8958. doi: 10.1021/acs.analchem.0c00925. Epub 2020 Jun 8.

Abstract

Hyperthyroidism-induced liver injury is quite common in clinical settings. Therefore, developing rapid and simple methods for the assessment of hyperthyroid liver injury is of great significance. Considering phosphorus metabolism is disordered because of hyperthyroidism, and the hyperthyroid liver injury is closely related to the abnormal level of glutathione (GSH). Thus, development of a new method that can simultaneously detect changes in blood phosphorus and GSH levels of serum, liver, kidney, and other organs to assess the degree of hyperthyroid liver injury is necessary for clinical medical research. Herein, a novel fluorescent metal-organic frameworks (MOFs) nanoprobe using the UiO-66(OH) as core and Cu-MOFs as shell was designed and synthesized. Through the specific action between Zr (IV) and phosphate, and the combine interaction of MOFs active center Cu (II) and GSH, high sensitivity and specific fluorescence detection of phosphate and GSH were achieved, respectively. Finally, the nanosensor was applied for evaluating different degrees of hyperthyroid liver injury in mice models and realized the monitoring of serum, liver, kidney, and other organs' blood phosphorus and GSH levels, and found that the levels of phosphate and GSH in serum were negatively correlated with the degree of hyperthyroid liver injury, while the changes of phosphate and GSH levels in the liver and kidney organs were positively correlated with the degree of hyperthyroid liver injury. In general, the present works provide a new way to effectively evaluate liver injury induced by hyperthyroidism in the early clinical stage.

摘要

甲状腺功能亢进症引起的肝损伤在临床实践中较为常见。因此,开发快速、简便的方法来评估甲状腺功能亢进性肝损伤具有重要意义。考虑到甲状腺功能亢进会导致磷代谢紊乱,而甲状腺功能亢进性肝损伤与谷胱甘肽(GSH)水平异常密切相关。因此,开发一种新的方法来同时检测血清、肝、肾等器官中血磷和 GSH 水平的变化,以评估甲状腺功能亢进性肝损伤的程度,对临床医学研究具有重要意义。在此,设计并合成了一种新型荧光金属有机骨架(MOFs)纳米探针,以 UiO-66(OH)为核,Cu-MOFs 为壳。通过 Zr(IV)与磷酸盐之间的特异性作用,以及 MOFs 活性中心 Cu(II)与 GSH 的结合相互作用,分别实现了对磷酸盐和 GSH 的高灵敏度和特异性荧光检测。最后,将纳米传感器应用于评估不同程度的甲状腺功能亢进症小鼠模型中的肝损伤,并实现了对血清、肝、肾等器官中血磷和 GSH 水平的监测,发现血清中磷酸盐和 GSH 的水平与甲状腺功能亢进性肝损伤的程度呈负相关,而肝和肾器官中磷酸盐和 GSH 水平的变化与甲状腺功能亢进性肝损伤的程度呈正相关。总之,本研究工作为有效评估早期临床阶段甲状腺功能亢进引起的肝损伤提供了一种新方法。

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