神经干细胞移植治疗APP／PS1小鼠磁共振波谱及行为学对照研究

目的应用氢质子磁共振波谱（Protonmagneticresonancespectroscopy，1H—MRS）技术及Mor-ris水迷宫（Morriswatermaze，MWM）检测，探讨神经干细胞（NSCs）移植治疗APP／PS1转基因阿尔茨海默病（Alzheimerdisease，AD）小鼠的效果。方法C57BL／6小鼠NSCs培养、扩增。12月龄APP／PS1转基因AD小鼠（实验组）30只与野生型小鼠（对照组，C组）15只作为实验对象。实验组小鼠随机数字表法分为A、B两组，分别移植NSCs（A组）及PBS（B组）至AD双侧海马CA1区，对照组不作处理。移植前及移植后4周行1H．MRS成像及MWM测试，并与组织病理学结果进行对照研究。结果1H—MRS显示移植前A、B及c组小鼠的NAA／Cr值分别为1．01±0．08、1．03±0．05及1．21±0．05，mI／Cr值分别为0．69＋0．05、0．71±0．06及0．58±0．06，A、B组间差异均无统计学意义（P〉O．05），但均较c组差异有统计学意义（P〈0．05）。移植4周后A组NAA／Cr值升高（1．18±0．09），mI／Cr值降低（0．53±0．04），均较B组相同时点差异有统计学意义（P〈0．05），与c组相比差异无统计学意义（Jp〉0．05）。行为学检测显示移植后A组逃避潜伏期明显缩短，较B组差异有统计学意义（P〈0．05）；移植后A组小鼠平台停留时间（35．21±5．44）S]、穿越平台次数（5．75±3．23）次]也较B组明显增加（P〈0．05）。Nissl＇s染色显示AD小鼠在NSCs移植后海马区神经元细胞数较未移植AD小鼠明显增多（P〈0．05）。结论NSCs移植可明显改善AD小鼠的学习、记忆能力，1H—MRS可从功能代谢水平有效的评价NSCs移植治疗AD的效果。

The experimental research between magnetic resonance spectroscopy and changes of behavior for neuralstem cell transplantation in APP/PS1 transgenic mice

Objective To explore the effect of neural stem cell（NSCs） transplantation on proton magnetic resonance spectroscopy （1H-MRS） and the behavior in APP/PS1 double transgenic AD mice. Methods NSCs from C57BL/6 mice were cultured and amplified. APP/PS1 double transgenie AD mice （n=30） aged 12 months were used as the study group,and mild-type mice （ n= 15） were used as the control group（group C ）. Animals in the study group were randomly divided into two subgroups：one receiving NSCs （group A） and the other receiving PBS transplantation （group B） in bilateral hippoeampal CA1 of the AD model mice. Animals in the group C were not treated. 1H-MRS and Morris water maze （MWM） were performed before transplantation and 4 weeks after transplantation, and compared with the histopathological results. Results 1H-MRS showed that there was no signifi- cant change in NAA/ Cr（ 1.01±0.08 and 1.03±0.05） and mI/Cr （0.69±0.05 and 0.71±0.06） ratios between group A and group B before transplantation （P〉 0.05） ,but the changes were significant compared with the group C （ NAA/ Cr： 1.21±0.05 ; mI/Cr：0.58±0.06） （P〈0.05）. Four weeks after transplantation, NAA/ Cr ratio（ 1.18± 0.09） was increased and mI/Cr ratio （0.53±0.04） was decreased in group A. The difference was significant com- pared with the group B at the same time points （P〈0.05）. MWM showed the escape latency in group A was signifi- cantly shorter than that in group B after transplantation （P〈O.05）. In addition, group A also showed an exclusive preference for the target quadrant,and spent more time（（35.21±5.44） s） in the 3rd quadrant compared with group B （P〈O.05）. For number of platform crossings,similar results were also shown（5.75±3.23）. Nissl＇s staining showed that the number of neurons in the hippoeampal area increased more significantly in group A than those in group B（P〈0. 05 ）. Conclusion NSCs transplantation can improve spatial learning and memory via neurons re- generation in APP/PS1 double transgenie AD mice,and 1H-MRS is able to display intracranial metabolite changes after NSCs transplantation.