Analysis of free radical reactions in diseases model animals using in vivo ESRI

使用体内 ESRI 分析疾病模型动物中的自由基反应

• 批准号: 15087206
• 负责人: USUMI Hideo
• 金额: $ 19.9万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15087206/
• 关键词: reactive oxygen species; free radical; redox; electron spin resonance; life-related diseases; cancer; molecular imaging; MRI; 潰瘍性大腸炎; 一酸化窒素; 活性窒素; 肝再生; 糖尿病; ポルフィリン症; 生体計測ESR; スピンプローブ; 酸化ストレス性疾患; 脳虚血再灌流

Free radical is reportedly associated with various diseases such as diabetes, hypertension, cerebrovascular accident, and cancer. In this study, we investigated the relationship between free radical generation and the initiation/development of diseases using in vivo ESR/spin probe technique. The ESR signal decay rate of MC-PROXYL, which is a membrane-permeable nitroxyl probe, in N-diethylnitrosoamine (DEN)-treated group is enhanced compared with that in control group, while the ESR signal decay rate of carbamoyl-PROXYL, which is a less membrane-permeable probe, in DEN-treated group is not changed, suggesting that reactive oxygen species is generated at the intracellular compartment of liver in DEN-treated rat.OMRI is a newly developed imaging apparatus, which enables us to get free radical images with higher space resolution and shorter measuring time. We developed the molecular imaging system that is to visualize the redox reactions between in cell and out of cell simultaneously with … More ^<14>N-or ^<15>N-labeled nitroxyl probes. Phantom objects containing ascorbic acid-encapsulated liposomes with membrane-permeable radicals but not membrane-impermeable ones show a time-dependent decrease of the OMRI image intensity. This OMRI system was applied to the in vivo free radical detection of experimental disease models such as NSAIDs-induced gastric ulcer and ulcerative colitis, and in vivo mapping of enhanced radical generation at the intra-cellular compartment and/or the extra-cellular compartment that was induced by the development of disease was obtainedHowever, the images of 0.015 T OMRI have low time and space resolution, resulting in the inaccurate anatomical information because its MRI magnetic field is too low. So, in this study sample transport OMRI system having 0.4 T was developed. The clear image of the phantom, which is composed of cylindrical grass tube (diameter 2.0 mm, wall thickness 0.35 mm) and rectangular container filled with nitroxyl radical solution, was obtained using this sample transport OMRI Less

据报道，自由基与各种疾病如糖尿病、高血压、脑血管意外和癌症有关。在这项研究中，我们研究了自由基的产生和疾病的发生/发展之间的关系，使用在体内ESR/自旋探针技术。与对照组相比，N-二乙基亚硝胺（DEN）处理组中膜渗透性硝酰基探针MC-PROXYL的ESR信号衰减速率增加，而膜渗透性较差的探针氨基甲酰基-PROXYL的ESR信号衰减速率没有变化，表明DEN处理的大鼠肝脏细胞内产生活性氧。OMRI是一种新开发的成像设备，这使我们能够获得更高的空间分辨率和更短的测量时间的自由基图像。我们开发了分子成像系统，该系统可以同时显示细胞内外的氧化还原反应， ...更多信息 N<14>-或N<15>-标记的硝酰基探针。含有抗坏血酸封装的脂质体与膜渗透性自由基，但不是膜不渗透的幻影对象显示的OMRI图像强度的时间依赖性降低。该OMRI系统应用于实验性疾病模型（如NSAID诱导的胃溃疡和溃疡性结肠炎）的体内自由基检测，并获得了由疾病发展诱导的细胞内和/或细胞外室的增强的自由基产生的体内绘图。然而，0.015 T OMRI图像的时间和空间分辨率低，由于其MRI磁场太低，导致解剖信息不准确。因此，在这项研究中，样品传输OMRI系统具有0.4 T的开发。利用该样品传输OMRI Less获得了由圆柱形草管（直径2.0 mm，壁厚0.35 mm）和填充有硝酰基自由基溶液的矩形容器组成的体模的清晰图像

项目成果

Matsumoto, S., Koshiishi, I., Inoguchi, T., Nawata, H., Utsumi, H.: "Confirmation of superoxide generation via xanthine oxidase in streptozotocin-induced diabetic mice"Free Radic Res. 37・7. 767-772 (2003)

Matsumoto, S.、Koshiishi, I.、Inoguchi, T.、Nawata, H.、Utsumi, H.：“链脲佐菌素诱导的糖尿病小鼠中黄嘌呤氧化酶产生超氧化物的确认”Free Radic Res 37・7-。 772（2003）

Utsumi, H., Yamada, K.: "In vivo electron spin resonance-computed tomography/nitroxyl probe technique for non-invasive analysis of oxidative injuries"Arch Biochem Biophys. 416・1. 1-8 (2003)

Utsumi, H., Yamada, K.：“用于氧化损伤非侵入性分析的体内电子自旋共振计算机断层扫描/硝酰基探针技术”Arch Biochem Biophys 416・1（2003）。

Evidence for contribution of vascular NAD(P)H oxidase to increased oxidative stress in animal models of diabetes and obesity.

• DOI: 10.1016/j.freeradbiomed.2004.04.001
• 发表时间: 2004-07
• 期刊: Free radical biology & medicine
• 影响因子: 7.4
• 作者: T. Sonta;T. Inoguchi;H. Tsubouchi;N. Sekiguchi;Kunihisa Kobayashi;S. Matsumoto;H. Utsumi;H. Nawata

Yonekura, Y., Koshiishi, I., Yamada, K., Mori, A., Uchida, S., Nakamura, T., Utsumi, H.: "Association between the expression of inducible nitric oxide synthase by chondrocytes and its nitric oxide-generating activity in adjuvant arthritis in rats"Nitric O

Yonekura, Y.、Koshiishi, I.、Yamada, K.、Mori, A.、Uchida, S.、Nakamura, T.、Utsumi, H.：“软骨细胞诱导型一氧化氮合酶表达与其硝酸盐之间的关联

In vivo oxygen radical generation in the skin of the protoporphyria model mouse with visible light exposure:: An L-band ESR study

• DOI: 10.1111/j.0022-202x.2004.22601.x
• 发表时间: 2004-06-01
• 期刊: JOURNAL OF INVESTIGATIVE DERMATOLOGY
• 影响因子: 6.5
• 作者: Takeshita, K;Takajo, T;Utsumi, H
• 通讯作者: Utsumi, H