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

• 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
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14207105/
• 关键词: reactive oxygen species; free radical; electron spin resonance; diabetes; obese; nitroxyl radical; 生体計測ESR; スピンプローブ; 循環器疾患; 無侵襲解析; 心不全; トランスジェニックマウス; reactive oxygen species; free radical; electron spin resonance; diabetes; obese; nitroxyl radical; 生体計測ESR; スピンプローブ; 循環器疾患; 無侵襲解析; 心不全; トランスジェニックマウス

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）参与循环疾病的主动性和/或进展。为了进行分析，我们使用硝基氧基自由基作为ROS产生指数的信号衰变速率开发了体内自旋电子共振（ESP）/自旋探针技术，并阐明了ROS在实验性动物中与多种疾病的关联。当静脉内给予疾病组的卡巴酰基羟基溶液（是硝基氧基自由基之一）时，与对照组相比，甲甲酰羟基的信号衰减速率得到了增强。 SOD和α-生育酚抑制了增强，这表明疾病组信号衰变的增强是由于血管中的ROS产生。此外，增强抑制了B…更多的Y蛋白激酶C抑制剂CGP41251和NADPH氧化物抑制剂Apocinin，这表明ROS的产生来自血管中的NADPH氧化物。它对于研究了在实验动物或组织中，我们构建了Esri/MRI Systems中的ROS生成ROS的生成至关重要。将具有不同膜渗透率的硝基自由基静脉内给予小鼠，然后进行ESRI/MRI测量。使用此成像系统阐明了血管中分布在血管和血管中和组织中的硝氧基自由基之间的自旋动态状态的差异。我们新合成了几种15N标记的硝基自由基， ^<15> N， ^<15> n， ^<15> n，d <15> n，d nitroxyl do nitroxyl Sadicals为了改善Esr Sensitivity。此外，我们开发了自动调整控制（ATC）和自动匹配控制（AMC），以抑制呼吸道或跳动噪声，并评估了Vivo ESR测量中的控制特性。我们阐明了糖尿病模型或肥胖动物模型的血管中的ROS产生。在不久的将来，通过应用ESRI/MRI融合系统和新合成的问题对ROS动态状态的图像分析将在循环疾病的倡议和/或进展中阐明ROS的产生。较少的