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使用体内二硝基苯酚磁共振成像(DNP-MRI)评估杜氏肌营养不良模型小鼠的氧化还原变化。

Evaluation of the redox alteration in Duchenne muscular dystrophy model mice using in vivo DNP-MRI.

作者信息

Eto Hinako, Murata Masaharu, Kawano Takahito, Tachibana Yoko, Elhelaly Abdelazim Elsayed, Noda Yoshifumi, Kato Hiroki, Matsuo Masayuki, Hyodo Fuminori

机构信息

Center for Advanced Medical Open Innovation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

Department of Radiology, Gifu University, 1-1 Yanagido, Gifu, 501-1194, Japan.

出版信息

Npj Imaging. 2024 Dec 5;2(1):52. doi: 10.1038/s44303-024-00058-8.


DOI:10.1038/s44303-024-00058-8
PMID:40603630
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12118763/
Abstract

Duchenne muscular dystrophy (DMD) is a genetic muscular disease and is the most common type of muscular dystrophy in Japan. Noninvasive magnetic resonance imaging (MRI) can be used for follow-up evaluation of myositis and muscular dystrophy, including DMD and inflammation is evaluated based on the increased muscle water as evaluated by T2-weighted MR images. However, in MDM, the redox status has not been evaluated non-invasively during the disease progression. We assessed the inflammation via the redox status in experimental animal disease models using in vivo dynamic nuclear polarization MRI (DNP-MRI) with a redox probe. The current study aimed to evaluate the skeletal muscle of mdx mice, a DMD model, in which muscle fiber necrosis, inflammation, and muscle regeneration were chronically repeated. Results showed that the reduction rate of Carbamoyl-PROXYL (CmP), one of the redox probes, radicals in mdx mice increased compared with that in normal mice. In vitro, more mitochondria or macrophages enhanced the radical form decay reaction by reducing CmP. Due to muscle fiber damage, the mdx mice had a lower mitochondrial concentration in the gastrocnemius muscle than the normal mice. However, the in vivo DNP-MRI results strongly reflected the increased reduction of CmP radicals by macrophages. In conclusion, in vivo DNP-MRI, a noninvasive imaging method is useful for locally evaluating skeletal muscle inflammation.

摘要

杜氏肌营养不良症(DMD)是一种遗传性肌肉疾病,在日本是最常见的肌营养不良症类型。无创磁共振成像(MRI)可用于对肌炎和肌营养不良症进行随访评估,包括DMD,并且基于T2加权磁共振图像评估的肌肉水分增加来评估炎症。然而,在MDM中,尚未在疾病进展过程中对氧化还原状态进行无创评估。我们使用氧化还原探针通过体内动态核极化MRI(DNP-MRI)在实验性动物疾病模型中通过氧化还原状态评估炎症。本研究旨在评估mdx小鼠(一种DMD模型)的骨骼肌,其中肌肉纤维坏死、炎症和肌肉再生长期反复发生。结果显示,与正常小鼠相比,mdx小鼠中氧化还原探针之一的氨基甲酰基-脯氨酰自由基(CmP)的还原率增加。在体外,更多的线粒体或巨噬细胞通过还原CmP增强了自由基形式的衰变反应。由于肌肉纤维损伤,mdx小鼠腓肠肌中的线粒体浓度低于正常小鼠。然而,体内DNP-MRI结果强烈反映了巨噬细胞对CmP自由基还原的增加。总之,体内DNP-MRI这种无创成像方法可用于局部评估骨骼肌炎症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa18/12118763/8e0b3890c10f/44303_2024_58_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa18/12118763/397c17c67814/44303_2024_58_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa18/12118763/90d8a953d7f3/44303_2024_58_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa18/12118763/8efbd6ac2bac/44303_2024_58_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa18/12118763/cc750dc68f18/44303_2024_58_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa18/12118763/8e0b3890c10f/44303_2024_58_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa18/12118763/397c17c67814/44303_2024_58_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa18/12118763/90d8a953d7f3/44303_2024_58_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa18/12118763/8efbd6ac2bac/44303_2024_58_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa18/12118763/cc750dc68f18/44303_2024_58_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/aa18/12118763/8e0b3890c10f/44303_2024_58_Fig5_HTML.jpg

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[1]
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J Neuromuscul Dis. 2023

[2]
Duchenne muscular dystrophy: disease mechanism and therapeutic strategies.

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[3]
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[4]
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[5]
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[6]
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Free Radic Biol Med. 2022-2-1

[7]
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Biomolecules. 2021-11-22

[8]
The Interplay of Mitophagy and Inflammation in Duchenne Muscular Dystrophy.

Life (Basel). 2021-7-4

[9]
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Am J Physiol Cell Physiol. 2021-8-1

[10]
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