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Real Time Analysis of Drug-Diffusion in Muscle with in vivo ESR-Spectroscopy

利用体内 ESR 光谱实时分析肌肉中的药物扩散

基本信息

批准号：
02670986
负责人：
HAMADA Akira
金额：
$ 1.54万
依托单位：
Showa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1992
项目状态：
已结题

项目摘要

In order to utilize in vivo ESR-CT for studying drug-distribution and free radical reaction in biological system, we tried to measure ESR spectra of nitroxides administered into femoral muscle in mice, and obtained the following results.1. Diffusion of spin-labeled compounds in muscle : Spin-labeled compound was injected into femoral muscle in mice.The resulting ESR spectrum seemed to be consisted of several components, which was due to different concentration of spin-labeled compound each other. Analysis of the spectrum with computer simulation indicated that the diffusion of nitroxide compounds in femoral muscle could be monitored with in vivo ESR. The signal of amino-TEMPO in femoral muscle of mice was decayed during occlusion, while that of Carbamoyl-PROXYL decreased only after reperfusion, suggesting that amino-TEMPO lose their paramagnetism in femoral muscle and Carbamoyl-PROXYL was transferred from muscle to blood.2. ESR-CT system : One dimensional imaging of nitroxide administered into femoral muscle of mice was performed, suggesting that in vivo ESR-CT system may be applied to the study of drug-delivery-system.3. Nitroxide reduction by ischemia-reperfusion injury : We prepared ischemia-reperfusion injury model by occlusion and reperfusion of the femoral thigh with a thread. The effects of ischemia-reperfusion on the reduction of nitroxides in femoral muscle were investigated by in vivo ESR, suggesting that nitroxides were reduced by active oxygen species produced by ischemia-reperfusion.4. Improvement of ESR-CT system : To analyze the ESR spectrum containing several signals, spectral-special imaging system was developed.

为了利用体内ESR-CT研究生物系统中的药物分布和自由基反应，我们尝试测量了氮氧化物在小鼠股骨肌肉中的ESR波谱，并获得了以下结果。自旋标记化合物在肌肉中的扩散：将自旋标记化合物注射到小鼠的股骨肌肉中，得到的ESR谱似乎是由几个组分组成的，这是由于自旋标记化合物彼此之间的不同浓度所致。计算机模拟光谱分析表明，体内电子自旋共振可以监测氮氧化合物在股骨肌肉中的扩散。结论：1.缺血后小鼠股肌氨基-TEMPO信号衰减，而氨甲酰-丙氧基仅在再灌流后才减弱，提示氨基-TEMPO在股肌失去顺磁性，氨甲酰-丙氧基转移到血液中。ESR-CT系统：对小鼠股肌内注射氮氧化物进行了一维成像，表明ESR-CT系统可应用于体内给药系统的研究。缺血再灌注损伤对一氧化氮的还原作用：用线栓法制作股大腿缺血再灌注损伤模型。通过体内ESR研究缺血再灌流对股骨肌内一氧化氮还原的影响，提示缺血再灌流产生的活性氧可以减少一氧化氮的生成。ESR-CT系统的改进：为了分析包含多个信号的ESR频谱，开发了频谱专用成像系统。