认知功能障碍大鼠脑神经型烟碱乙酰胆碱受体显像研究

采用双侧颈总动脉结扎法建立大鼠慢性脑缺血模型,4周后经Morris水迷宫实验验证认知功能障碍,经尾静脉注射神经型烟碱乙酰胆碱受体(nAChRs)显像剂2-~(18)F]-A-85380后30、60、120、180、240min,用Micro-PET各扫描一次,每次持续10 min。选取丘脑、额皮质、小脑为鼠脑感兴趣区,以SUV_(ave丘脑)/SUV_(ave小脑)、SUV_(ave额皮质)/SUV_(ave小脑)放射性摄取比为慢性缺血组与正常组的比较参数。经正常组大鼠扫描后,慢性脑缺血认知障碍大鼠选择在120 min行2-~(18)F]-A-85380 Micro-PET脑部扫描10min。结果表明,Morris定向航行实验中两组大鼠逃避潜伏期随实验天数增加而缩短,在第5d时正常组为(9.44±5.48)s,慢性缺血组为(24.16±27.18)s,差异有统计学意义,慢性缺血组大鼠在学习寻找平台上较正常组缓慢;Morris空间探索实验,撤掉平台后,慢性缺血鼠按之前学习寻找平台的轨迹,穿过原来放置平台的象限次数较正常组少,慢性缺血组为(2.60±1.67)次,正常组为(6.20±2.95)次,差异有统计学意义;正常大鼠脑部Micro-PET显像,在120min时,可清晰显示丘脑、小脑及额皮质结构,且持续至240min,其SUV_(ave丘脑)/SUV_(ave小脑)、SUV_(ave额皮质)/SUV_(ave小脑)放射性摄取比在120 min时分别为1.62±0.06、1.34±0.28,认知功能障碍大鼠SUV_(ave丘脑)/SUV_(ave小脑)、SUV_(ave额皮质)/SUV_(ave小脑)放射性摄取比分别为1.27±0.02、1.07±0.03,差异有统计学意义。通过对缺血大鼠进行2-~(18)F]-A-85380 MicroPET脑显像发现,2-~(18)F]-A-85380在慢性缺血大鼠与正常大鼠的丘脑相比摄取降低,缺血组SUV_(ave丘脑)/SUV_(ave小脑)、SUV_(ave额皮质)/SUV_(ave小脑)较正常组显著降低,说明缺血后认知功能障碍与烟碱乙酰胆碱受体减少有关。缺血后认知功能障碍大鼠能在出现运动症状前出现受体数量降低或2-~(18)F]-A-85380与受体结合率降低,通过nAChRs受体显像可在慢性缺血后已出现认知障碍的患者中发现其受体早期变化,从而给予早期干预治疗,改善预后。

The Quantitative Analysis of 2-[18F]-A-85380 nAChRs Micro-PET Brain Imaging in Chronic Ischemic Rats with Cognitive Dysfunction in Vivo

The change of 2-18F]-A-85380 in chronic ischemia rats with cognitive dysfunction was evaluated by Micro-PET.Chronic cerebral ischemia rat model was made by bilateral common carotid artery ligation.Four weeks later,Morris water experiments were performed to check cognitive dysfunction.After intravenous injection of 37 MBq 2-18F]-A-85380,the normal isoflurane-anesthetized rat underwent Micro-PET scan.The brain scanning was performed for 10 minutes at 30,60,120,180,240 minutes after injection.Select the thalamus,frontal cortex,cerebellum as region of interesting for quantitative analysis.The chronic ischemia rats underwent Micro-PET scan for 10 minutes at 120 minutes.SUVave tha1amus /SUVave cerebcellum,SUVave frontal cortex /SUVave cerebellum were calculated.Four weeks after the surgical procedure,Morris water maze was used to assess working memory tasks with two groups of rats.The escape latency of the chronic ischemia group and the normal group at the fifth day was (24.16±27.18) s,(9.44±5.48) s,respectively.The chronic ischemia group compared with the normal group,the difference was statistically significant.The ischemic group in learning to find the platform slower than the normal rats.At the sixth day,the chronic ischemia rats by looking for the original platform quadrant after removed the platform,was slower than the normal group in Morris space exploration experiments.The chronic ischemia group was (2.60±1.67)times,the normal group was (6.20±2.95) times,the difference was statistically significant.By the Micro-PET scanning,the thalamus could be distinguished markedly during 120 minutes to 240 minutes,especially at 120 minutes.At 120 minutes,SUVave thalamus / SUVave cerebellum,SUVavefrontalcortexp /SUVave cerebellum of the chronic ischemia cognitive dysfunction rats was 1.27±0.02,1.07±0.03,respectively.The SUVave thalamus /SUVave cerebellum,SUVavefronta1cortex /SUVave cerebellum of the nomal group was 1.62 ± 0.06 and 1.34 ± 0.28,respectively.The difference was statistically significant.2-18F]-A-85380 is suitable for nAChRs imaging.The suitable time for rats Micro-PET imaging in vivo was 120～240 minutes,especially at 120 minutes.The quantitative analysis of nAChRs in different brain regions of rats was performed in vivo,which is very useful for detecting the changes of variety receptors in chronic ischemia cognitive dysfunction rats,meanwhile lay the foundation for investigating chronic ischemia cognitive dysfunction rats in various stages or evaluating the efficacy of treatment in chronic ischemia cognitive dysfunction rats.