【作者】 何婷婷；

【导师】 田嘉禾；

【作者基本信息】 中国人民解放军军医进修学院 ， 影像医学与核医学， 2008， 硕士

【摘要】 [目的]建立阿尔茨海默病（AD）大鼠模型后进行神经干细胞（NSCs）移植治疗,以正常组、模型组、移植组的行为学、组织学改变为标准,探讨¹¹C-PIB和¹⁸F-FDG显像在模型验证及监测细胞移植中的应用价值,有望为AD的诊断治疗研究提供在体的、可视化的技术平台。[方法]建立Aβ（1-40）海马注射的AD大鼠模型,通过行为学及组织学改变验证模型成功后进行¹¹C-PIB PET和¹⁸F-FDG micro PET成像,观察图像结果是否与行为学、组织学结果相匹配。对造模成功的大鼠进行细胞移植,比较模型组与移植组行为学、组织学改变,同时进行¹¹C-PIB和¹⁸F-FDG显像,观察显像结果是否与行为学、组织学结果相匹配。[结果]模型组在Morris水迷宫中的潜伏期明显长于正常组（P＜0.01）,组织学显示海马CA₁及齿状回出现神经元丢失和Aβ沉积,¹¹C-PIB显像中模型组海马区域PIB放射性摄取明显增高（P＜0.05）,¹⁸F-FDG显像中模型组海马注射侧的放射性摄取明显低于对侧和正常组的同侧（P＜0.001）,显像结果与行为学、组织学结果匹配。细胞移植后移植组潜伏期较模型组减少33.7%～51.5%（P＜0.01）,组织学显示Aβ沉积无明显改变,NSCs分化表达ChaT、GFAP、NeuN阳性细胞,并持续6周表达Brdu阳性细胞,¹¹C-PIB显像表明移植组与模型组放射性摄取无显著差异（P＞0.05）,显像结果与Aβ沉积相匹配,与行为学、细胞分化结果不匹配。¹⁸F-FDG显像表明移植组与模型组海马注射侧的放射性摄取基本一致（P＞0.05）,显像结果同样与行为学、细胞分化结果不匹配。[结论]¹¹C-PIB和¹⁸F-FDG显像有助于诊断AD和活体监测AD模型的病理学改变,但目前尚不能为AD干细胞移植的疗效监测提供一安全、动态、在体的可视化工具。更多还原

【Abstract】 [Purpose]Established rat model of Alzheimer’s disease（AD）and grafted neural stem cells（NSCs）,choosing the changes of behavior test and histology of normal group,model group and transplantation group as the reference standard, discussing the value of ¹¹C-PIB and ¹⁸F-FDG imaging in model verification and cell transplantation monitoring,hoping to providing the visualed technology method in vivo for the research of AD’s diagnose and therapy.[Methods]Established the Aβhippocampus injected rat model,verified by behavior test and histology,then performed ¹¹C-PIB PET and ¹⁸F-FDG micro PET imaging and observed whether the result of imaging was matched with behavior test and histology’s.Grafted NSCs to the successful rat model,comparing the changes of behavior test and histology between model group and transplantation group,then performing the ¹¹C-PIB and ¹⁸F-FDG imaging,observing whether the result of imaging was matched with behavior test and histology’s[Result]The Morris water maze improved that the escaped latent period of model group was longer than that of normal group（P＜0.01）,in histology neuron loss and Aβdeposition were found in hippocampus CAl and dentate gyrus of rat model, ¹¹C-PIB imaging showed increased uptake in model rat hippocampus district （P＜0.05）,¹⁸F-FDG imaging showed that the uptake in hippocampus inject district of model group was lower than that of normal group（P＜0.001）,there was also much different uptake between bilateral hippocampus of model group（P＜0.001）, these results were matched with behavior test and histology.After cell transplantation,the escaped latent period of transplantation group was shorter than that of model group（P＜0.01）,which reduced 33.7%～51.5%,in histology there was no much change in Aβdeposition,NSCs differentiated and expressed ChaT、GFAP、NeuN positive cells,and expressed Brdu positive cells for six weeks, ¹¹C-PIB imaging showed there was no much change in hippocampus district between model group and transplantation group（P＞0.05）,which was matched with Aβdeposition,but not matched with results of behavior test and cell differentiation of histology.¹⁸F-FDG imaging showed there was no much chang in injected hippocampus of the two groups（P＞0.05）,the result was not matched with the behavior test and cell differentiation of histology..[Conclusion]¹¹C-PIB and ¹⁸F-FDG imaging can be the ideal of AD diagnose and monitoring the pathological change of AD model in vivo.But it can not provide a safe,dynamic,in vivo imaging tool for monitoring therapeutic effect of implant stem cell for AD at present.更多还原