| Project/Area Number |
14207105
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Kyushu University |
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Principal Investigator |
UTSUMI Hideo KYUSHU UNIVERSITY, Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学研究院, 教授 (20101694)
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| Co-Investigator(Kenkyū-buntansha) |
TAKESHITA Akira KYUSHU UNIVERSITY, Graduate School of Medical Sciences, Emeritus Professor, 大学院・医学研究院, 名誉教授 (30038814)
YASUI Hisataka KYUSHU UNIVERSITY, Graduate School of Medical Sciences, Emeritus Professor, 大学院・医学研究院, 名誉教授 (20089923)
KOGA Noboru KYUSHU UNIVERSITY, Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学研究院, 教授 (60161890)
HIRATA Hiroshi Yamagata University, Department of Engineering, Associate Professor, 工学部, 助教授 (60250958)
INOGUCHI Toyoshi KYUSHU UNIVERSITY, Graduate School of Medical Sciences, Assistant Professor, 大学院・医学研究院, 講師 (00294926)
輿石 一郎 九州大学, 薬学研究院, 助教授 (20170235)
門司 晃 九州大学, 医学研究院, 助手 (00294942)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥50,440,000 (Direct Cost: ¥38,800,000、Indirect Cost: ¥11,640,000)
Fiscal Year 2004: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
Fiscal Year 2003: ¥14,690,000 (Direct Cost: ¥11,300,000、Indirect Cost: ¥3,390,000)
Fiscal Year 2002: ¥26,520,000 (Direct Cost: ¥20,400,000、Indirect Cost: ¥6,120,000)
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| Keywords | 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 |
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| Research Abstract |
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
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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
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