磁性标记的小胶质细胞在大鼠脑内的MR示踪

Magnetic resonance tracking of transplanted microglia labeled with superparamagnetic iron oxide particles in the brain of normal rat and Alzheimer＇s disease model rat

目的探讨超顺磁性氧化铁颗粒（SPIO）标记的小胶质细胞在正常大鼠及阿尔茨海默病（AD）大鼠体内移植后，MR活体示踪的可行性。方法以日本血液凝集病毒包膜（HVJ-E）为标记载体，将SPIO标记的小胶质细胞经颈内动脉注入正常大鼠（5只）及AD大鼠动物模型（5只）体内，3d后应用7．0TMR行T2^＊序列扫描，并与脑组织切片组织化学染色结果对照。结果在正常大鼠脑内，MRI可见数个点状的信号改变区，这些信号改变区散在地分布在脑内各处，脑组织切片显示铁颗粒标记细胞位置与信号改变部位一致。MRI能够检测到由数个标记细胞引起的信号强度的改变。在AD大鼠模型脑内，MRI可见β-淀粉样蛋白42（Aβ42）注射区信号强度明显下降，信号改变区面积较大。与之相比，生理盐水注射区信号改变的强度及面积均不如Aβ42注射区改变明显。Aβ42注射区的标记细胞数为（454±47）个／mm^2，明显高于生理盐水注射区的标记细胞数（83±13）个／mm^2（P〈0．05）。结论MRI可作为一种非侵人性检测手段在活的动物体内追踪标记细胞，在AD细胞水平的治疗中具有一定临床应用前景。

Objective To explore the methods of labeling exogenous microglia with superparamagnetic iron oxide （SPIO） particles, and to monitor the labeled ceils after transplantation into the normal rat and Alzheimer＇s disease （AD） model rat with MR scanning. Methods Microglia was labeled with SPIO particles by using transfection agent, hemagglutinating virus of Japan envelope （HVJ-E）. Then the microglias which were labeled with SPIO were injected into the internal carotid artery of normal rat （ n = 5 ） and AD model rat （ n = 5 ）. Three days after transplantation, follow-up serial T2^＊ -weighted gradient-echo MR imaging was performed at 7.0T MRI system. MR images were correlated with histological findings. Results In the brain of normal rat, the labeled microglias were demonstrated as several dotty signal intensity decrease on T2^ ＊ -weighted MR images. The dotty spots were sporadic around the brain. Histological analysis showed that most prussian blue staining-positive ceils were well correlated with the area where a signal intensity decrease was observed in MRI. MR could detect the signal intensity change caused by a few labeled ceils. In the brain of AD model rat, MR scan showed a well-defined hypointensity area in the region of Aβ42 injection. Signal intensity decrease was not obvious in the region of saline injection. The number of iron-positive cells （454 ± 47 ）/mm^2 at sites of Aβ42 injection was much higher than that （83 ± 13 ）/mm^2 of saline injection （ P 〈 0. 05 ）. Conclusion MR can be used as a non-invasive means of detecting transplanted labeled microglia in vivo, with the potential for future clinical application in cell therapy of AD.