Nitroxide-enhanced magnetic resonance imaging of kidney dysfunction in vivo based on redox-imbalance and oxidative stress

Nitroxide-enhanced magnetic resonance imaging of kidney dysfunction in vivo based on redox-imbalance and oxidative stress
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DOI:
10.4149/gpb_2019001
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发表时间:
2019-01-01
影响因子:
1.5
通讯作者:
Bakalova, Rumiana
Bakalova, Rumiana
中科院分区:
生物学4区
文献类型:
--
作者:
Lazarova, Dessislava;Shibata, Sayaka;Bakalova, Rumiana

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本研究报告了一种基于肾组织氧化还原失衡和氧化应激诱导的无创性磁共振成像(MRI)方法,该方法以Mito-Tempo作为氧化还原敏感的对比探针。肾功能障碍是由高胆固醇血症引发的。小鼠被分成三组:(I)正常饮食(ND);(Ii)胆固醇饮食(CD);(Iii)胆固醇+胆碱胺饮食(CC)。饲养15周后,对小鼠进行以下分析:血浆胆固醇水平;肾脏功能的血清检测;体内组织氧化还原状态的氮氧化物增强磁共振成像;组织切片的组织化学染色以显示肾脏损伤;对分离的组织标本进行总抗氧化能力和氧化应激的评估。肾脏MITO-TEMPO的MRI信号特征为:CD组高信号、寿命长,提示肾脏组织氧化能力强;ND组信号弱、寿命短,还原能力强;CC组信号中等、寿命较短,提示降脂药物的保护作用。这些数据在分离的组织样本上得到了证实,使用的是常规测试。他们认为,高胆固醇血症导致肾脏氧化还原失衡,这一过程可以用MRI和mito-tembo作为氧化还原敏感的对比来可视化。
This study reports a non-invasive magnetic resonance imaging (MRI) of kidney dysfunction in mice, based on the induction of redox-imbalance and oxidative stress in the renal tissues, using mito-TEMPO as redox-sensitive contrast probe. Kidney dysfunction was triggered by hypercholesterolemia. The mice were divided in three groups: (i) on normal diet (ND); (ii) on cholesterol diet (CD); (iii) on cholesterol plus cholestyramine diet (CC). After 15 weeks feeding, the mice were subjected to the following analyses: plasma cholesterol levels; serum test for renal functionality; nitroxide-enhanced MRI of tissue redox-status in vivo; histochemical staining of tissue section to visualize renal damage; evaluation of total antioxidant capacity and oxidative stress on isolated tissue specimens. MRI signal of mito-TEMPO in the kidney was characterized by: high intensity and long life-time in CD mice, indicating a high oxidative capacity of renal tissues; poor intensity and short life-time in ND mice, indicating a high reducing capacity; moderate intensity and relatively short life-time in CC mice, indicating a protective effect of lipid-lowering drug. The data were confirmed on isolated tissue specimens, using conventional tests. They suggest that hypercholesterolemia induces redox-imbalance in kidney and this process could be visualized using MRI and mito-TEMPO as a redox-sensitive contrast.