Non-invasive analysis of dynamic state of reactive oxygen species in tissue and blood vessel of circulatory diseases

无创分析循环系统疾病组织及血管活性氧动态

基本信息

批准号：
14207105
负责人：
UTSUMI Hideo
金额：
$ 32.28万
依托单位：
Kyushu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

It is reported that reactive oxygen species (ROS) are involved in the initiation and/or progression of circulatory diseases. In order to analyze is vivo ROS generation non-invasively, we developed the In vivo spin electron resonance (ESP)/spin probe technique using a signal decay rate of a nitroxyl radical as an index of ROS generation and clarified the association of ROS generation with several diseases in experimental animals.In this study, we performed non-invasive measurement of ROS generation in the models of diabetes and obese as representative circulatory diseases. When carbamoyl-PROXYL solution, which is one of nitroxyl radicals, was administered intravenously to the disease group, the signal decay rate of carbamoyl-PROXYL was enhanced compared with the control group. The enhancement was suppressed by SOD and α-tocopherol, suggesting that the enhancement of signal decay in the disease group is due to ROS generation in blood vessels. Furthermore, the enhancement was suppressed b … More y protein kinase C inhibitor, CGP41251 and NADPH oxidase inhibitor, apocinin, suggesting that ROS generation is derived from NADPH oxidase in the blood vessels.It is essential to investigate ROS generates in what organ or tissue of experimental animals, we built the ESRI/MRI fusion system. Nitroxyl radicals with different membrane permeability were intravenously administered to mice, and then the ESRI/MRI measurement was performed. The difference of the spin dynamic state between nitroxyl radicals distributing in blood vessels and those in not only blood vessels but also tissues were clarified using this imaging system.We newly synthesized several kinds of 15N-labeled nitroxyl radicals and ^<15>N, D-labeled nitroxyl radicals in order to improve ESR sensitivity. Furthermore, we developed the automatic tuning control(ATC) and the automatic matching control(AMC) for the purpose of the suppression of respiratory or beating noise and evaluated the control characteristics in in vivo ESR measurement.We clarified the ROS generation in blood vessels of animal models of diabetes or obese. In the near future, the image analysis of ROS dynamic state with high sensitivities by the application of the ESRI/MRI fusion system and the newly synthesized probes would be clarified the ROS generation in the initiation and/or progression of circulatory diseases. Less

据报道，活性氧（ROS）参与循环系统疾病的发生和/或进展为了非侵入性地分析体内ROS的产生，我们开发了体内自旋电子共振（ESP）/自旋探针技术。使用硝酰基自由基的信号衰减率作为ROS生成的指标，并阐明了实验动物中ROS生成与多种疾病的关联。在本研究中，我们在糖尿病和肥胖模型中进行了ROS生成的无创测量代表性的当向疾病组静脉注射硝酰基自由基之一的氨基甲酰-PROXYL溶液时，与对照组相比，氨基甲酰-PROXYL的信号衰减率增强，而SOD和α-生育酚抑制了这种增强。，表明疾病组信号衰减的增强是由于血管中 ROS 的产生，此外，y 蛋白激酶 C 抑制剂抑制了这种增强， CGP41251和NADPH氧化酶抑制剂apocinin，表明ROS的产生来源于血管中的NADPH氧化酶。研究ROS在实验动物的哪些器官或组织中产生是至关重要的，我们用硝酰基自由基构建了ESRI/MRI融合系统。给小鼠静脉注射不同的膜渗透性，然后进行ESRI/MRI测量硝酰基之间的自旋动态状态的差异。使用该成像系统澄清了分布在血管中以及分布在血管和组织中的自由基。为了改善ESR，我们新合成了几种15N标记的硝酰基自由基和^<15>N，D标记的硝酰基自由基此外，我们还开发了用于抑制呼吸或搏动噪声的自动调谐控制（ATC）和自动匹配控制（AMC），并评估了体内ESR的控制特性。我们阐明了糖尿病或肥胖动物模型血管中ROS的生成，在不久的将来，通过应用ESRI/MRI融合系统和新合成的探针，可以对ROS动态进行高灵敏度的图像分析。阐明了循环系统疾病的发生和/或进展中ROS的产生。