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磁共振成像在体可视化检测肾脏5-羟色胺的动态变化及药物性急性肾损伤早期无创诊断

In vivo visualization of renal serotonin dynamics using magnetic resonance imaging for early non-invasive diagnosis of drug-induced acute kidney injury

  • 摘要: 【目的】磁共振成像(MRI)在体检测肾脏5-羟色胺受体的动态变化,为药物性急性肾损伤早期诊断提供无创影像方法。【方法】以5-羟色胺基团为基础,构建具有5-羟色胺受体靶向性的磁共振对比剂(HT-Gd),通过检测小鼠肾脏部位T1加权磁共振成像(T1WI)信号,探索药物性肾损伤早期MRI检测方法。【结果】体外细胞内吞试验发现,经顺铂预处理12 h后,肾小管上皮细胞(HK-2)对HT-Gd的摄取是36.8 pg/cell,而未经顺铂处理细胞对HT-Gd摄取量仅为14.7 pg/cell。在体内磁共振成像研究中发现,HT-Gd可以增强顺铂给药24 h小鼠的肾脏T1WI信噪比至40.5%,约为未经顺铂处理组小鼠的2倍(SNR=20.2%)。【结论】HT-Gd可视化检测肾脏部位的5-羟色胺受体,实现了对顺铂诱导急性肾损伤的早期诊断,为药物性急性肾损伤早期诊疗研究提供了新的参考方法。

     

    Abstract: 【Objective】 Magnetic resonance imaging(MRI) was employed to monitor the real-time alterations in renal serotonin receptors in vivo, presenting a non-invasive imaging technique for the prompt identification of drug-induced acute kidney injury.【Method】 A magnetic resonance contrast agent(HTGd) engineered with serotonin receptor-targeting capabilities was developed based on the serotonin group.By analyzing the T1-weighted magnetic resonance imaging(T1WI) signals of serotonin receptors in mouse kidneys, an early MRI detection approach was investigated for the identification of drug-induced kidney injury.【Result】 In vitro endocytosis experiments revealed that the uptake of HT-Gd by renal tubular epithelial cells(HK-2) was 36. 8 pg/cell following a 12-hour cisplatin pretreatment, contrasting with a mere 14. 7 pg/cell uptake in cells devoid of cisplatin treatment. In vivo magnetic resonance imaging studies demonstrated that HT-Gd heightened the renal T1WI signal-to-noise ratio to 40. 5% in mice subjected to cisplatin treatment for 24 hours, approximately double that of mice not treated with cisplatin(SNR=20. 2%).【Conclusion】 The visualization of serotonin receptors in the kidney using HT-Gd has enabled the early diagnosis of cisplatin-induced acute kidney injury, offering a novel reference technique for the early diagnosis and treatment exploration of drug-induced acute kidney injury.

     

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