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

据报道，活性氧（ROS）参与了循环系统疾病的发生和/或进展。为了无创地分析体内ROS生成，我们开发了体内自旋电子共振(ESP)/自旋探针技术，以硝基自由基的信号衰减率作为ROS生成的指标，并在实验动物中阐明了ROS生成与几种疾病的关系。在本研究中，我们在糖尿病和肥胖作为代表性循环系统疾病的模型中进行了ROS生成的无创测量。疾病组静脉给予氨酰基- proxyl溶液，与对照组相比，氨酰基- proxyl信号衰减率增强，氨酰基- proxyl是一种硝基自由基。这种增强被SOD和α-生育酚抑制，提示疾病组信号衰减的增强是由于血管中ROS的生成。此外，CGP41251和NADPH氧化酶抑制剂apocinin抑制了这种增强，表明ROS的产生来源于血管内的NADPH氧化酶。为了研究ROS在实验动物的哪些器官或组织中产生，我们建立了ESRI/MRI融合系统。小鼠静脉注射不同膜透性的硝基自由基，进行ESRI/MRI测量。利用该成像系统，明确了分布于血管内的氧基自由基与既存在于血管又存在于组织内的氧基自由基自旋动态的差异。为了提高ESR的灵敏度，我们新合成了几种15n标记的硝基自由基和^<15>N， d标记的硝基自由基。此外，我们开发了自动调谐控制（ATC）和自动匹配控制（AMC）以抑制呼吸或跳动噪声，并评估了体内ESR测量中的控制特性。我们明确了糖尿病或肥胖动物模型血管中ROS的生成。在不久的将来，应用ESRI/MRI融合系统和新合成的探针对ROS动态进行高灵敏度的图像分析，将有助于阐明循环系统疾病发生和/或发展过程中ROS的产生。少

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