| 嵇建峰,刘蕴莹,孔月,谷庆.18F-FDG micro-PET代谢显像评估大鼠放射性认知功能障碍的实验研究[J].中华放射医学与防护杂志,2020,40(9):653-658 |
| 18F-FDG micro-PET代谢显像评估大鼠放射性认知功能障碍的实验研究 |
| Experimental study in the evaluation of radiation-induced cognitive dysfunction in rats via 18F-FDG micro-PET metabolic imaging |
| 投稿时间：2020-02-21 |
| DOI：10.3760/cma.j.issn.0254-5098.2020.09.001 |
| 中文关键词: 2-18F-2-脱氧-D-葡萄糖微型正电子发射断层显像 全脑照射 认知障碍 海马 c-Fos |
| 英文关键词:18F-FDG micro-PET Whole-brain irradiation Cognitive dysfunction Hippocampus c-Fos |
| 基金项目:国家自然科学基金（81602672）；浙江省医药卫生科研项目（2019324448，2019327308） |
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| 中文摘要: |
| 目的 研究大鼠放射性脑损伤模型中葡萄糖代谢与神经元活性的相关性，探讨2-18F-2-脱氧-D-葡萄糖（18F-FDG）micro-PET用于放射性认知功能障碍评估的潜在价值。方法 将3周龄雄性SD大鼠按照随机数表法分成对照组以及全脑照射组，每组10只，脑照射组利用小动物精确放疗仪给予10 Gy X射线照射，对照组不予照射。通过Morris水迷宫（MWM）实验评估大鼠认知功能，对两组大鼠脑部micro-PET图像数据进行对比分析，免疫组织化学染色检测神经元活性标记物c-Fos蛋白在脑内的表达变化，免疫荧光染色检测幼稚神经元标志物DCX及新生成熟神经元标志物BrdU/NeuN阳性细胞数的变化。结果 照射3个月后，与对照组相比，全脑照射的大鼠在MWM定向航行实验中第2至4天的潜伏期均显著延长（t=2.179、3.393、3.219，P<0.05），MWM空间探索实验中的目标象限的探索时间百分比减少（t=3.857，P<0.01），提示全脑照射可引起海马依赖性认知能力下降；SPM分析micro-PET图像显示全脑照射组海马区域葡萄糖代谢显著降低（t=5.12，P<0.05）；此外，全脑照射组海马区域神经元活性标记蛋白c-Fos的表达显著减少（t=14.22，P<0.01），幼稚神经元标志物DCX及新生成熟神经元标志物BrdU/NeuN阳性细胞数均较对照组减少（t=18.77、9.304，P<0.01）。结论 全脑放疗后海马区域的葡萄糖代谢减低，与海马神经元活性下降及神经发生减少相一致，表明18F-FDG micro-PET可以作为评估放射性认知功能障碍的有效方法。 |
| 英文摘要: |
| Objective To investigate the correlation between glucose metabolism and neuron activity in radiation-induced brain injury of rat, and to explore the potential implication of 18F-FDG micro-PET in the assessment of radiation-induced cognitive dysfunction. Methods Three-week-old male Sprague-Dawley (SD) rats were divided into two groups, whole-brain irradiation (WBI) group and non-irradiation control group, according to the random number table method. The WBI group was irradiated with 10 Gy X-rays using a small animal precise radiotherapy apparatus. Morris water maze (MWM) test was performed to evaluate the cognitive capability of rats. 18F-FDG micro-PET covering the whole brain was conducted and the micro-PET images were processed by SPM software. The expression of neuronal activity marker c-Fos protein in rat brain was detected by immunohistochemical staining. The neuronal precursors marker DCX positive cells and newborn mature neurons marker BrdU/NeuN positive cells were detected by immunofluorescence staining. Results Three months after irradiation, MWM place navigation test showed that the latency of whole-brain irradiated rats was longer than that of the control group (t=2.179, 3.393, 3.219, P<0.05). In MWM spatial probe test, the percentage of target quadrant exploring time was reduced in the WBI group compared with the control group (t=3.857, P<0.01). These result suggested that WBI caused hippocampus injury-related cognitive decline. SPM analysis of micro-PET images showed that, after WBI, the glucose metabolism in the hippocampus was significantly reduced (t=5.12, P<0.05), the neuronal active marker c-Fos protein expression was significantly downregulated (t=14.22, P<0.01), and the neuronal precursors marker DCX positive cells and newborn mature neurons marker BrdU/NeuN positive cells were both decreased (t=18.77, 9.304, P<0.01). Conclusions Glucose metabolism in the hippocampus was reduced after WBI, in consistent with the decrease of neuron activity and the reduction of neurogenesis in this area, suggesting that 18F-FDG micro-PET could be an effective method for assessing radiation-induced cognitive dysfunction. |
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