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Non-invasive evaluation of free radical reactions accompanied with induction and development of heart failure by in vivo ESR-CT

通过体内ESR-CT无创评估伴随心力衰竭诱发和发展的自由基反应

基本信息

批准号：
12470526
负责人：
UTSUMI Hideo
金额：
$ 9.41万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12470526/
关键词：
in vivo ESR-CT free-radical spin-probe reactive oxygen species reactive nitrogen species redox balance failing myocardium スピンプローブ活性酸素種心筋梗塞拡張型心筋症

项目摘要

Failing myocardium is a final stage of several types of heart diseases, and the prognosis is the similarly worst as malignant tumor. Therefore, an establishment of preventive method should be essential. Recently, participation of free radicals belonging to reactive oxygen species and reactive nitrogen species in the induction and development of failing myocardium through in vivo cross-talk among free radicals and collapse of redox balance was indicated.In order to evaluate the fluctuation of redox balance in individuals, it is best way to evaluate temporal-spatial fluctuation of free radical reactions by imaging techniques. In our latest study, we established in vivo ESR-CT system using nitroxyl spin probes, and applied it to non-invasive evaluation of free radical reactions in living mice with several types of diseases. This technique is usable for elucidating a correlation between free radical reactions and failing myocardium in individual organism level and molecular level.In the present study, we examined a participation of free radicals in the induction and development of failing myocardium using model dogs. As a result, we proved that free radical generation was significantly enhanced, while activities of anti-oxidant enzymes did not fluctuated. Through this experiment, we elucidated that electron transfer system in mitochondria is a main source of these free radicals. In fact, there is a significantly negative correlation between the regeneration of transplanted heart and the degree of free radical generation. On the other hand, we established a novel algorithm for imaging of free radicals in individual, and succeeded to simultaneously determined reactive oxygen species and reactive nitrogen species.

心肌衰竭是多种心脏病的终末期，其预后与恶性肿瘤一样差。因此，建立预防方法是必不可少的。近年来研究表明，活性氧和活性氮类自由基通过体内自由基间的相互作用和氧化还原平衡的破坏参与了心肌衰竭的发生和发展，而利用影像学技术评价自由基反应的时空波动是评价个体氧化还原平衡波动的最佳方法。本课题组建立了硝酰基自旋探针体内ESR-CT系统，并将其应用于多种疾病活体小鼠自由基反应的无创性评价。该技术可用于阐明个体生物水平和分子水平上的自由基反应与心肌衰竭之间的相关性。结果表明，自由基的产生显著增强，而抗氧化酶的活性没有波动。通过本实验，我们阐明了线粒体内的电子传递系统是这些自由基的主要来源。事实上，移植心脏的再生与自由基生成程度呈显著负相关。另一方面，我们建立了一种新的自由基成像算法，并成功地同时测定了活性氧和活性氮。