Nuclear magnetic resonance study on the evaluation of energy metabolism in the brain in vivo-A case of rat brain intoxicated with methymercury-

体内脑能量代谢评价的核磁共振研究-以甲基汞中毒大鼠脑为例-

基本信息

批准号：
04454219
负责人：
MITSUMORI Fumiyuki
金额：
$ 3.84万
依托单位：
National Institute for Environmental Studies
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04454219/
关键词：
NMR Methylmercury Brain Energy metabolism ATP Phosphocreatine

项目摘要

In spite of great efforts to elucidate the toxicity of organic mercury, the molecular and cellular mechanism of the toxicity remains still unclear. In the present study we focused on the effect of methylmercury on energy metabolism in brain, and conducted an NMR investigation aiming at evaluation of oxidative capacity in the brain in vivo. The following results have been obtained.1. A rat model of methylmercury poisoning was established by oral administration of 5mg Hg/kg body weight methylmercury daily for 12 days.2. A phosphorus-31 NMR measurements were successfully carried out to observe high energy phosphorus metabolites from the brain avoiding signal contamination from the surrounding muscles and skins by a combination of a surface coil probe and a surgical operation.3. In the methylmercury poisoned brain the steady state concentration of ATP was maintained normal, but that of phosphocreatine (PCr) was reduced to 4.78 mumolg^<-1> compared with the normal concentration of 5.48mumolg^<-1>.4. An ATP turnover rate both in the normal and poisoned brain was 0.22 mumolg^<-1> sec^<-1> from the ^<31>P NMR saturation transfer measurement.5. Oxidative phosphorylation capacity in in vivo brain was evaluated from the steady state PCr level and the ATP turnover rate assuming a Michaelis-Menten equation controlled by ADP on the oxidative phosphorylation reaction. The result demonstrated that the oxidative capacity in the poisoned brain was approximately 15% reduced compared with the normal brain.6. We are also developing a technique of proton localization spectroscopy for rat brain to observe metabolites which are not phosphorylated.

尽管为阐明有机汞的毒性做出了巨大努力，但毒性的分子和细胞机制仍然不清楚。在本研究中，我们着重于甲基汞对大脑能量代谢的影响，并进行了NMR研究，旨在评估体内大脑的氧化能力。已经获得以下结果。1。每天通过口服5mg hg/kg体重甲基汞，建立了甲基汞中毒的大鼠模型，持续12天。成功进行了磷-31 NMR测量值，以观察大脑的高能磷代谢物，避免了周围肌肉和皮肤的信号污染，并结合了表面线圈探针和手术手术。3。在甲基汞中毒的大脑中，ATP的稳态浓度保持正常，但与正常浓度为5.48mumolg^<-1> .4相比，磷酸蛋白（PCR）的稳态浓度降低至4.78 mumolg^<-1>。正常和中毒大脑中的ATP周转率均为0.22 mumolg^<-1> sec^<-1>，从^<31> p NMR饱和转移测量值5。从稳态PCR水平和ATP周转率评估了体内脑中的氧化磷酸化能力，假设ADP控制了ADP对氧化磷酸化反应控制的Michaelis-Menten方程。结果表明，与正常脑相比，中毒大脑中有毒大脑的氧化能力降低了15％。6。我们还为大鼠脑开发了一种质子定位光谱技术，以观察未磷酸化的代谢产物。