Noninvasive assessment of the brain redox status in chronic kidney disease mouse using overhauser-enhanced magnetic resonance imaging

使用奥豪瑟增强磁共振成像对慢性肾病小鼠的脑氧化还原状态进行无创评估

• 批准号: 20790039
• 负责人: YAMATO Mayumi
• 金额: $ 2.75万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20790039/
• 关键词: イメージング; グルタミン酸; 脳; 腎不全; レドックス

Urea toxin is suggested to be induced the glutamatergic neuronal damage mediated by the activity of N-methyl-D-aspartate (NMDA) receptor. In this study, we aimed to demonstrate brain redox alterations in chronic kidney disease mouse noninvasively, using overhauser-enhanced magnetic resonance imaging (OMRI).The reduction rate of 3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-l-oxyl (methoxycarbonyl-PROXYL), a redox-sensitive contrast agent, was used as an index of the redox status in vivo. No changes were seen in the 8-OHdG (8-Hydroxydeoxyguanosine) or the memory disturbance at 2 or 4 weeks after CKD onset, but after 4 weeks of CKD, the methoxycarbonyl-PROXYL reduction rate, calculated from continuous images, had increased significantly. At 8 weeks after CKD onset, we observed an increase in the number of 8-OHdG-immunopositive cells and the disturbance in the memory. Thus, the noninvasive imaging of the brain redox alterations was associated with the initial stages of CKD cause brain injury.

尿素毒素被认为可诱导 N-甲基-D-天冬氨酸 (NMDA) 受体活性介导的谷氨酸能神经元损伤。在本研究中，我们旨在利用奥豪瑟增强磁共振成像（OMRI）无创性地证明慢性肾病小鼠的脑氧化还原变化。氧化还原敏感造影剂3-甲氧基羰基-2,2,5,5-四甲基吡咯烷-l-氧基（甲氧基羰基-PROXYL）的还原率被用作指标 体内氧化还原状态。 CKD 发病后 2 周或 4 周时，8-OHdG（8-羟基脱氧鸟苷）或记忆障碍未见变化，但 CKD 4 周后，根据连续图像计算得出的甲氧羰基-PROXYL 减少率显着增加。 CKD 发病后 8 周，我们观察到 8-OHdG 免疫阳性细胞数量增加，记忆力紊乱。因此，脑氧化还原变化的无创成像与 CKD 导致脑损伤的初始阶段相关。