MR显微成像检测活体阿尔茨海默病转基因小鼠老年斑沉积的效果

目的利用MR显微成像技术研究阿尔茨海默病转基因小鼠老年斑的沉积情况。方法2只17个月龄阿尔茨海默病转基因[V717I]小鼠和2只野生型小鼠，行活体T2WI，然后对照影像定位结果进行组织学切片及免疫组织化学染色。观察T2WI中老年斑的沉积情况以及其与免疫组织化学染色结果的对应关系。结果转基因小鼠T2WI上显示大脑皮层和海马区可见点状低信号，且部分低信号可以和组织学切片所显示的老年斑相对应；野生型小鼠T2WI未见明显的低信号，免疫组织化学染色也未见到染色阳性的斑块。结论MR显微成像技术检测老年斑的沉积是可行的，且可用来特异性地诊断阿尔茨海默病。     

穿膜肽介导的超微超顺磁性纳米铁颗粒体外标记神经干细胞的实验观察

利用干细胞的多潜能特性进行移植和替代研究是再生医学的重要内容,利用磁性纳米颗粒对干细胞进行标记并进行磁共振实时动态监测是一种非常有前景的干细胞示踪方法[1-3],我们试图通过对超小型超顺磁性纳米铁颗粒(ultrasmall superparamagnetic iron oxide,USPIO)进行表面修饰后连接Tat穿膜肽,探讨这种方法能否将USPIO带人干细胞内,旨在为干细胞的磁共振示踪寻找一条新途径.     

靶向纳米铁磁共振造影剂特异性标记阿尔茨海默病鼠脑内老年斑

目的 开发具有高度特异性的靶向磁共振对比剂,验证其特异性显示阿尔茨海默病(AD)脑内老年斑的可能性及有效性.方法 利用热分解法获得水相的磁性纳米四氧化三铁颗粒(MNPs),经过表面官能化学修饰,完成MNPs与β淀粉样蛋白肽段1-40(Aβ40)及蛋白质转导结合域(protein transduction domain,Tat-PTD)的连接后,制备出特异性与老年斑相结合的靶向纳米铁造影剂Aβ40-MNPs-Tat PTD,通过尾静脉注射人20只AD鼠和20只阴性对照C57小鼠(4、6、9、12月龄各5只)体内,不同的时间点采用7.0 T动物磁共振检测获得磁共振图像,观察靶向纳米造影剂对脑实质内老年斑信号的强化效果,继之处死小鼠后灌流取脑做连续冰冻切片,进行铁染色和Thioflavine S染色组织学验证.结果 所获得的靶向纳米颗粒Aβ40-MNPs-Tat PTD能够在体外进入细胞内进而改变细胞磁共振T2信号强度.尾静脉注射入AD鼠体内后能特异性负性强化AD鼠脑内老年斑病变,经组织学验证,能够与老年斑染色及铁染色相对应.结论 特异靶向性的磁性纳米铁造影剂Aβ40-MNPs-Tat PTD能特异性地针对小鼠脑内的老年斑病变进行负性强化和标记.

Abstract：

Objective To develop specific targeted magnetic biomarkers which can selectively mark the senile plaques in Alzheimer' s disease (AD) and verify its feasibility and validity.Methods Aβ1-40 peptide and Tat-PTD ( Tat-protein transduction domain) was binded with dextran-coated ultrasmall superparamagnetic iron oxide ( USPIO) particles.Visualization of plaques in vivo in Alzheimer transgenic mice was investigated at 7.0 Tesla using T2 sequences after intravenous administration of the targeted nanoiron contrast agent and verified by histological staining.Results The targeted nano-iron contrast agent could enter the cultured neural stem cells,and was able to accelerate T2 relaxation rates of water protons in the cells and negatively reinforce the T2 signal intensity in the labeled cells.Plaques were specifically detected in vivo by magnetic resonance imaging ( MRI) and correlated well with histological staining after injection of nano-iron contrast agent into the APP/PS1 mice.Conclusion The targeted nano-iron contrast agent has the ability of selectively labeling the senile plaques in AD brain tissues in vivo,which might enable the early detection of plaques by MRI and can be further applied in the studies of early diagnosis of AD.